Substituted phthalides and heterocyclic phthalides

ABSTRACT

Substituted phthalides and heterocyclic phthalides and derivatives thereof which are useful as herbicides are described.

This is a Continuation of application Ser. No. 08/201,150, filed on Feb. 23, 1994, now U.S. Pat. No. 5,506,192 which is a Continuation of application Ser. No. 08/036,006, filed Mar. 23, 1993, now abandoned, which is a Continuation-In-Part of application Ser. No. 07/804,150, filed Dec. 6, 1991, now abandoned, which is a Continuation-In-Part of application Ser. No. 07/633,592, filed Dec. 21, 1990, now abandoned, which is a Continuation-In-Part of application Ser. No. 07/534,794, filed Jun. 7, 1990, now abandoned.

The present invention concerns substituted phthalides and heterocyclic phthalides and derivatives thereof, processes for their production, compositions containing them and their use in agriculture.

More particularly, the invention concerns compounds of formula I ##STR1## wherein ring system A is selected from c) pyrazinyl-N-oxide

d) pyrimidinyl

e) pyrazinyl

f) 3- or 4- cinnolynyl or 2-quinoxalinyl, and

g) a five membered heteroaromatic ring comprising oxygen, sulphur or nitrogen as heteroatom(s) which ring may be fused to a benzene ring or may comprise nitrogen as an additional heteroatom.

R is cyano, formyl, CX₁ X₂ X₃, a ketone forming group, a carboxyl group which may be in the form of the free acid or in ester or salt form, a thio-carboxyl group which may be in the form of the free acid or in ester form, a carbamoyl group or a mono- or di-substituted carbamoyl group, hydroxyalkyl, hydroxybenzyl, --CH═NOH, --CH═NO-lower alkyl, the group --CH₂ --O--C(O)-- which bridges adjacent carbon atoms in ring A, or a ring C ##STR2## Y₁, Y₂ and Y₃ are attached to carbon atoms and are independently hydrogen, halogen, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylsulfonyloxy, dialkylsulfamoyloxy, alkylsulfonyl, alkylsulfinyl, dialkylcarbamoyloxy, alkylthio, alkenylthio or alkynylthio each of which may in turn be substituted by 1 to 6 halogen atoms; dialkoxymethyl, conjugated alkoxy, hydroxyalkyl, carboxyl, acyl, acylalkyl, acyloxy, acyloxyalkyl, trialkylsilyloxy, trialkylsilyl, cyano, nitro, amino or substituted amino, aminosulfonyl; cycloalkyl, aryl, aralkyl, aralkenyl, aralkynyl, aryloxy, aralkoxy, arylsulfonyl, arylsulfinyl, arylthio or aralkylthio, each of which may be substituted by one to three substituents selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, cyano, alkylthio, acyl, amino or substituted amino; a group ##STR3## wherein R' is hydrogen, lower alkyl, or lower alkoxy; or Y₁ and R taken together on adjacent carbon atoms form a bridge having the formula ##STR4## wherein E is a direct bond or a 1 to 3 membered linking group with elements selected from methylene, substituted methylene, ##STR5## and oxygen, or Y₁ and Y₂ taken together on adjacent carbon atoms form a 3- to 5-membered bridge comprised of elements selected from methylene, substituted methylene, ##STR6## oxygen, and ##STR7## each of W₁, W₂, W₃, W₄ and W₅ is independently CH, CR₃ or nitrogen; W₆ is NH, oxygen, sulfur, ##STR8## Z is a 2- or 3-membered bridge comprised of elements selected from methylene, substituted methylene, ##STR9## --N═, oxygen and ##STR10## R₁ and R₃ each is independently hydrogen; halogen; alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkenylthio or alkynylthio, each of which may in turn be substituted by 1 to 6 halogen atoms; cycloalkyl, heterocycloalkoxy, aryloxy, aralkoxy or aralkylthio each of which may be substituted by 1 to 3 substituents selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, cyano, alkylthio, acyl, amino or substituted amino; aminoxy; substituted aminoxy; iminoxy; substituted iminoxy; amino; substituted amino; amido; substituted amido; alkylsulfonylmethyl; cyano; nitro; or ##STR11##

wherein Y₄ is hydrogen, lower alkyl, lower alkoxy, hydroxy or unsubstituted or substituted phenyl.

R₄ is as defined for Y₁ except for hydrogen.

X and Y each is independently hydrogen, hydroxy, halogen, cyano, nitro, alkyl, alkoxy, alkoxycarbonyl, alkoxycarbonyloxy, hydroxyalkyl, haloalkyl, acyl, acyloxy, carbamoyl, carbamoyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl or alkylsulfonyloxy; aryl, aryloxy, arylS(O)p, aralkyl, aralkoxy, aralkS(O)_(p), arylsulphonyloxy, each of which may in turn be substituted by 1 to 3 substituents selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, cyano, alkylthio, acyl; amino, substituted amino or together represent ═O, ═S , ═NH, ═NOR₁₂ or ═CR₁₃ R₁₄ ; or

X and R together may form a bridge having the formula --O--E--, ##STR12## wherein the carbonyl is attached to A, E is defined above and R₂ represents hydrogen, hydroxy, alkyl, haloalkyl, alkoxyalkyl, alkoxy, aralkoxy, unsubstituted or substituted aryl, unsubstituted or substituted aralkyl or is as otherwise defined for R₇ hereinafter.

P is 0, 1 or 2.

X₁, X₂ and X₃ are independently hydrogen, hydroxy, alkoxy, alkylthio, hydroxyalkyl or hydroxybenzyl whereby at least one of X₁, X₂ and X₃ is other than hydrogen; or X₃ represents hydrogen and X₁ and X₂ together form a four or five membered bridge comprising elements selected from --O(CH₂)_(n),O--, ##STR13## and --S(CH₂)_(n),S--. R₁₂ is hydrogen or alkyl,

R₁₃ and R₁₄ are independently hydrogen, alkyl or halogen,

m is one or two,

n' is two or three

with the proviso that when R is carboxyl in free ester or salt form and X and Y together are ═O one of rings A and B contains a hetero atom.

When R is a ketone forming group this is preferably ##STR14## where R" is alkyl, haloalkyl, alkoxyalkyl, alkenyl, alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted aralkyl.

When R is a carboxyl or thio-carboxyl group in ester form it is preferably of formula --COOR₅ or --COSR₅ wherein R₅ is alkyl, haloalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, unsubstituted or substituted aryl, unsubstituted or substituted aralkyl, hydroxyalkyl, cycloalkyl, cyanoalkyl, aralkoxyalkyl; a group --N═C(R₁₅)(R₁₆); a group --(CH₂)_(n), CH(R₁₇)(R₁₈); a group ##STR15## R₁₅ and R₁₆ are independently hydrogen or alkyl, R₁₇ and R₁₈ are independently S(O)_(n) alkyl, COOR₉, alkoxy, amino, substituted amino, benzyloxy, trimethylsilyl, cyano, --C(R₁₉)SR₂₀ or additionally one thereof may be hydrogen.

R₁₉ is hydrogen or alkyl,

R₂₀ is alkyl or aryl,

R₉, R₁₀ and R₁₁ are independently hydrogen, alkyl, haloalkyl, alkoxyalkyl, unsubstituted or substituted aryl or unsubstituted or substituted aralkyl,

n and n" are independently zero, one or two, and

X₄ is oxygen or sulfur.

When R is a carbamoyl group or a mono- or di-substituted carbamoyl group it is preferably of formula CONR₇ R₈ wherein R₇ and R₈ are independently hydrogen or an aliphatic or a saturated or unsaturated cyclic or heterocyclic group each of which may be unsubstituted or substituted.

R₇ and R₈ are preferably each independently a) hydrogen; halogen; b) alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkoxy, alkenyloxy, alkynyloxy, alkylS(O)_(p), alkenylS(O)_(p) or alkynylS(O)_(p), alkylS(O)_(p) alkyl, alkenylS(O)_(p) alkyl, alkylnylS(O)_(p) alkyl, each of which may in turn be substituted by 1 to 6 halogen atoms or hydroxy and each of which may be attached to the adjacent nitrogen atom via alkyl; c) acyl, acylalkyl, acyloxy or acyloxyalkyl; d) cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, heterocycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, arylS(O)_(p), aralkylS(O)_(p) or arylS(O)_(p) alkyl, each of which is unsubstituted or may be substituted by 1 to 3 substituents selected from (i) halogen; (ii) alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkoxy, alkenyloxy, alkynyloxy, alkylS(O)_(p), alkenylS(O)_(p) or alkynylS(O)_(p), alkylS(O)_(p) alkyl, alkenylS(O)_(p) alkyl, alkynylS(O)_(p) alkyl, each of which may in turn be substituted by 1 to 6 halogen atoms; and (iii) nitro, cyano, acyl, amino or substituted amino, aminosulfonyl; aminoalkyl or substituted aminoalkyl; e) amino, substituted amino, amido, substituted amido; aminosulfonyl, cyano, nitro; or ##STR16## wherein Y₄ ' is hydrogen, lower alkyl, lower alkoxy or hydroxy and n'" is 0, 1, 2 or 3, and

p is 0, 1 or 2.

R₄ ' is as defined for Y₁.

X or Y as carbamoyl is also preferably of formula CONR₇ R₈ as defined above.

When R is carboxyl in salt form the salt is preferably formed with an alkali metal, alkali earth metal, optionally substituted ammonium cation, a trialkyl sulfonium cation, a trialkylsulfoxonium cation or a phosphonium cation, especially the cation of an alkali metal (e.g. the Li or Na cation) or of an earth alkali metal (e.g. the Ca or Mg cation); the ammonium cation; a substituted ammonium cation [such as a C₁₋₅ alkylammonium cation, a di-C₁₋₅ alkylammonium cation, a tri-C₁₋₅ alkylammonium cation, a tetra-C₁₋₅ ammonium cation, a (C₁₋₅ alkoxy-alkyl)ammonium cation, a (hydroxy-C₁₋₅ alkyl)ammonium cation]; a phosphonium cation; a tri(C₁₋₈ alkyl)sulfonium cation; or a tri(C₁₋₈ alkyl)sulfoxonium cation.

When Y₁, Y₂ and/or Y₃ is a carboxyl group this may be in ester or salt form or in amide form (i.e. a carbamoyl) and as such is as described above for R in these forms. Where A has meaning g) it contains one to three heteroatoms and signifies for example thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl or thiadiazolyl.

Where A has one of the above defined heteroaromatic significances, b) through g), the substituted hetero ring is particularly selected from pyridyl, quinolyl, pyridyl-N-oxide, pyrimidinyl, pyrazinyl, thienyl or furyl, more particularly from pyridyl or thienyl.

Alkyl moieties unless otherwise specified contain 1 to 8 carbon atoms, preferably 1 to 5, especially 1 to 4, e.g. 1 or 2 carbon atoms. Lower alkyl moieties contain 1 to 4, e.g. 1 or 2 carbon atoms. Alkyl moieties as are present in R₅, R₇ or R₈ contain 1 to 24 preferably 1 to 12, especially 1 to 6 carbon atoms whereby one of R₇ and R₈ is preferably hydrogen when the other is alkyl.

Alkyl moieties as bridging groups may be straight chain or branched and preferably contain 1 to 4, e.g. 1 or 2 carbon atoms. They may be optionally substituted by aryl or substituted aryl and may optionally be interrupted by or attached via an oxygen or sulfur atom.

"Conjugated alkoxy" stands for an alkoxy group interrupted in its alkyl moiety by one or more oxygen atoms eg alkoxyalkoxy, alkoxyalkoxyalkoxy, etc.

Alkenyl and alkynyl moieties contain 2 to 8, preferably 2 to 4, especially 2 or 3 carbon atoms.

Halogen is preferably F, Cl or Br, especially Cl

Aryl moieties are preferably as defined for meanings a) to g) of ring system A or as ring B and preferred meanings of each, especially phenyl. Such aryl moieties may be unsubstituted or substituted and in the latter case carry 1 to 3 substituents as defined for Y₁ unless otherwise specified. Substituted amino, -amido, -aminoxy, -aminoalkyl, -iminoxy, -carbamoyl (other than as R) is preferably substituted by one or two substituents selected from alkylalkoxy, haloalkl, acyl, alkoxyalkyl, unsubstituted or substituted aryl or unsubstituted or substituted aralkyl.

Substituted methylene is preferably substituted by one or two groups as defined for Y₁.

Acyl as or as part of a substituent is conveniently ##STR17## wherein R'" is as defined for Y₁ [for example alkyl, haloalkyl, cycloalkyl, alkoxyalkyl, unsubstituted or substituted aryl (especially phenyl)]. Examples of acyl include acetyl, propionyl, butyryl, unsubstituted or substituted benzoyl, pivaloyl or chloracetyl, especially acetyl or unsubstituted or substituted benzoyl.

Cycloalkyl is preferably of 3 to 6 carbon atoms especially cyclopropyl, cyclopentyl or cyclohexyl, heterocyclo is preferably 5 or 6 membered and as defined for A definitions b) to g) and preferences or saturated and containing O, S or N as heteroatom, eg tetrahydrofuryl, piperidinyl, morpholinyl.

For convenience bridging members such as ##STR18## are so written but are to be understood as embracing ##STR19##

Carbamoyl or substituted carbamoyl moieties are attached to the molecule which they substitute via their carbonyl. Amido or substituted amido moieties are attached to the molecule which they substitute via their nitrogen atom.

A particular group of compounds of formula I (compounds Ia) comprises those wherein ring system A is selected from phenyl, pyridyl or pyridyl-N-oxide.

R is a carboxyl group which may be in the form of the free acid or in ester or salt form, a thiocarboxyl group which may be in the form of the free acid or in ester form, a carbamoyl group or a mono- or di-substituted carbamoyl group.

Y₁, Y₂ and Y₃ are attached to carbon atoms and are independently hydrogen, halogen, alkyl, alkoxy;

each of W₁, W₂, W₃, W₄ and W₅ is independently CH, CR₃ or nitrogen;

W₆ is NH or oxygen;

Z is a 2- or 3-membered bridge comprised of elements selected from methylene, substituted methylene or ##STR20## R₁ and R₃ each is independently hydrogen, halogen, alkyl, alkoxy, aryloxy or aralkoxy.

X and Y each is independently hydrogen, hydroxy, cyano, alkoxy, acyloxy or together represent ═O; or

X and R together form a bridge having the formula ##STR21## wherein the carbonyl is attached to A.

When R is carboxyl or thio-carboxyl in ester form it is preferably of formula --COOR₅ or COSR₅ ;

wherein each R₅ is independently alkyl, alkoxyalkyl, alkenyl, alkynyl, substituted aryl or unsubstituted or substituted aralkyl.

When R is carboxy or thiocarboxyl in salt form the salt is preferably formed with an alkali metal, alkali earth metal, optionally substituted ammonium cation especially the cation of an alkali metal (e.g. the Li or Na cation) or of an earth alkali metal (e.g. the Ca or Mg cation); the ammonium cation; a substituted ammonium cation [such as a C₁₋₅ alkylammonium cation, a di-C₁₋₅ alkylammonium cation, a tri-C₁₋₅ alkylammonium cation, a tetra-C₁₋₅ ammonium cation.

When R is carbamoyl or mono- or di-substituted carbamoyl it is preferably of formula CONR₇ R₈ wherein R₇ is hydrogen, alkyl, haloalkyl, alkoxyalkyl, unsubstituted or substituted aryl or unsubstituted or substituted aralkyl and R₈ is hydrogen, alkyl, NH₂, NHR₆ or OR₆ wherein R₆ is as defined for R₇.

A particular compound group (compounds Ib) comprises those compounds of formula I wherein ring system A represents phenyl, pyridyl or thienyl; B represents pyrimidinyl or triazinyl; R represents a ring C especially oxazole, oxazolone, oxazolidine or oxazolidinone; carboxyl in the form of the free acid or in ester or salt form; substituted carbamoyl, cyano or together with X represent ##STR22## Y₁, Y₂ and Y₃ each represent independently hydrogen, halogen, alkyl, alkoxy, alkylthio or arylthio.

X, Y each represent independently hydrogen, hydroxy, alkoxy, acyloxy, a ring B, halogen, alkylthio or arylthio or together ═O or ═NH

and R₁ and R₃ each represent independently halogen, alkoxy, alkyl, haloalkoxy, optionally substituted aryloxy, aralkoxy, alkylnyloxy, alkenyloxy.

A further compound group comprises compounds Ib wherein Y₁, Y₂ and Y₃ additionally may each represent independently aralkoxy, alkenyloxy or alkynyloxy.

B is especially pyrimidinyl, particularly 4,6-dimethoxy-2-pyrimidinyl.

A is especially phenyl or pyridyl substituted as defined above.

X and Y are preferably hydrogen, halogen, cyano, hydroxy, alkoxy or together ═O, especially hydrogen, hydroxy or together ═O.

A further group of compounds according to the invention (Compounds Ic) comprises those of formula I wherein ring system A is pyridyl,

R is CONR₇ 'R₈ '

wherein R₇ ' and R₈ ' represent independently hydrogen, alkoxy, alkyl; or aryl or aralkyl each of which may be unsubstituted or substituted,

X is hydrogen,

Y is OR₃ ', SR₃ ' or OCOR₃ '

wherein R₃ ' is alkyl; or aryl; or aralkyl each of which may be unsubstituted or substituted,

or X and Y together represent ═O or ═S and ring system B is m-CF₃ phenyl.

Within the group Ib, compounds are preferred wherein X is OH and Y is H or X and Y together represent ═O, A is 2- or 3-pyridyl, R₇ is hydrogen or alkyl especially methyl, R₈ is phenyl or benzoyl which may be unsubstituted or substituted eg 1-3 times by halogen, alkyl and/or alkoxy.

The following meanings are preferred independently for each substituent.

A

a) meanings a) and b)

b) phenyl

c) pyridyl

R

a) carboxyl in the form of the free acid or in salt or ester form or carbamoyl or mono- or di-substituted carbamoyl

b) COOR₅ wherein R₅ is hydrogen, alkyl, COO⁺ Ma⁻ wherein Ma is an alkali metal or ammonium cation or CONR₇ R₈ wherein R₇ is hydrogen or alkyl and R₈ is alkyl, aryl or substituted aryl

c) COO⁻ Na⁺, COOCH₃, CONHC₆ H₁₃, CONH(CH₃)phenyl, COO⁻ H₃ N⁺ iC₃ H₇, CON(CH₃)₂, CONHCH₃

Y₁

a) hydrogen, halogen, alkyl or alkoxy

b) halogen, especially fluorine or chlorine

Y₂, Y₃

a) hydrogen or halogen, alkyl or alkoxy

b) hydrogen or halogen

c) chlorine

W₁ N

W₂

a) CH or N

b) CH

W₃ CR₃

W₄ N

W₅

a) CH or N

b) N

W₆

a) O

b) NH

Z

a) elements selected from methylene, substituted methylene, ##STR23## b) ##STR24## X₁, X₂ a) alkoxy, especially methoxy

b) hydroxy

X₃

a) hydrogen

b) alkoxy especially methoxy

R₁, R₃

a) alkoxy, especially methoxy

R₄

a) halogen, especially chlorine

b) alkyl, especially methyl

R₂

a) alkyl, especially methyl

b) hydrogen

R₅

a) alkyl, alkenyl or alkynyl

b) C₁₋₄ alkyl, especially methyl or ethyl

c) C₂₋₄ alkenyl

d) C₂₋₄ alkynyl, especially propargyl

R₆, R₇

a) alkyl

b) methyl, ethyl

R₈

a) hydrogen

b) alkyl, especially methyl or ethyl

c) an aryl, especially a phenyl

R₉, R₁₀,

a) hydrogen or alkyl

R₁₂, R₁₅, R₁₉

b) hydrogen or methyl

R₁₁

a) alkyl

b) propyl (n-- or iso--)

Y₄

a) alkyl or alkoxy

b) CH₃ or CH₃ O

R₁₃, R₁₄

a) hydrogen or halogen

b) hydrogen or fluorine

R₁₆

a) alkyl

b) C₁₋₄ alkyl, especially methyl or ethyl

R₁₇

a) S(O)_(n) alkyl or COOR₉

b) SO₂ CH₃ or COOCH₃

R₁₈

a) hydrogen

R₂₀

a) alkyl or phenyl

b) methyl or phenyl

n

a) 2 b) 0

n'

a) 2 b) 3

n"

a) 1 b) 0

m

a) 1 b) 2

X

a) hydroxy

b) hydrogen

c) taken with Y, ═O

d) acyloxy

e) alkoxycarbonyloxy

f) carbamoyloxy

g) sulphonyloxy

Y

a) taken with X, ═O

b) hydrogen ##STR25## X+R R'

a) alkyl b) alkoxy

R"

a) alkyl

b ) methyl

R'"

a) alkyl

b) aryl, especially phenyl

Ring A, Ring B

a) at least one contains a heteroatom

b) ring A=a phenyl or a pyridine

ring B=a pyrimidine especially 3,5 dimethoxy pyrimidine

Combinations Of the above listed preferred meanings are especially preferred. One such combination comprises compounds of formula (I) in which

A is phenyl or pyridyl;

R is a carboxyl group in the form of a free acid, ester or salt; carbamoyl: especially COOR₅ " wherein R₅ " is C₁₋₅ alkyl or C₂₋₅ alkenyl or CONR₇ "R₈ " wherein

R₇ " is C₁₋₁₂ alkyl, amino, C₁₋₄ alkylamino, anilino, haloanilino, benzyl, halobenzyl, C₁₋₄ alkylbenzyl, C₁₋₄ alkoxybenzyl, phenyl, halophenyl, C₁₋₄ alkylphenyl or C₁₋₄ alkoxyphenyl;

R₈ " is hydrogen or C₁₋₄ alkyl;

Y₁, Y₂ and Y₃ are independently hydrogen or halogen;

W₁ and W₄ are N;

W₂ is CH;

W₃ is CR₃ wherein R₃ is C₁₋₅ alkoxy;

R₁ is C₁₋₅ alkoxy;

X is hydroxyl or C₁₋₄ alkoxycarbonyloxy or taken with Y is ═O;

Y is hydrogen or taken with X is ═O; or

X and R together form a bridge having the formula --C(O)O-- wherein the carbonyl is attached to A, and Y is hydrogen or C₂₋₈ acyloxy.

A further group of compounds includes those of formula I wherein X may additionally represent COOR₅ as defined above; and/or R₁₅ and R₁₆ may additionally independently represent halogen, alkylthio, alkoxycarbonyl or optionally substituted carbamoyl; and/or R₁₈ may additionally represent optionally substituted aryl.

Further preferred substituent meanings include compounds according to claim 1 wherein A is other than phenyl, naphthyl, pyridyl which may be fused on its (b) or (c) side to benzene, or pyridyl-N-oxide.

Compounds according to claim 1 wherein R is other than formyl, a carboxyl group which may be in the form of the free acid or in ester or salt form, a thiocarboxyl group which may be in the form the free acid or in ester form or the group CX₁ X₂ X₃.

Compounds according to claim 1 wherein R is other than formyl, dimethoxymethyl, COOR₃₀ or COSR₃₁ wherein R₃₀ represents hydrogen, an alkali metal cation, an alkaline earth metal cation, an ammonium cation, an alkylammonium cation, C₁₋₃ alkyl, C₂₋₃ haloalkyl, allyl, propargyl, benzyl optionally substituted by halogen, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, methylthio, methylsulfinyl, methylsulfonyl or nitro, C₂₋₄ alkoxyalkyl, N═CR₃₂ R₃₃, CH₂ S(O)_(t) R₃₄ or CH(CH₃)S(O)_(t) R₃₄ wherein R₃₂ is chlorine, methyl, ethyl or methylthio, R₃₃ is methyl, ethyl, COOCH₃, COOC₂ H₅ or C(O)N(CH₃)₂, R₃₄ is methyl, ethyl, propyl, isopropyl or phenyl optionally substituted by halogen, methyl, methoxy or nitro and t is 0, 1 or 2; and R₃₁ represents methyl, ethyl or benzyl.

Compounds of formula I wherein A is pyridyl or pyridyl-N-oxide and at least two of Y₁, Y₂ and Y₃ are other than hydrogen.

Compounds of formula I wherein one of Y₁, Y₂ and Y₃ is other than hydrogen, fluorine, chlorine, methyl, methoxy, methylthio, methylsulfinyl or methylsulfonyl.

Compounds of formula I wherein A is phenyl and one of Y₁, Y₂ and Y₃ is other than hydrogen, fluorine, chlorine, methyl, ethyl, methoxy, ethoxy, C₂₋₃ alkenyl, C₂₋₃ alkynyl, SO.sub.(t) CH₃, SO.sub.(t) C₂ H₅, nitro, phenoxy, C₁₋₄ alkylcarbonyl, C(OCH₃)₂ CH₃ or C(SCH₃)₂ CH₃ and t is 0, 1 or 2.

Compounds of formula I wherein each of Y₁, Y₂ and Y₃ is other than hydrogen.

Compounds of formula I wherein one of W₁ and W₄ is other than nitrogen.

Compounds of formula I wherein W₂ is other than nitrogen or CH.

Compound of formula I wherein R₁ is other than methoxy or ethoxy.

Compound of formula I wherein W₃ is other than CR₃ wherein R₃ is methyl, ethyl, methoxy, ethoxy, difluormethoxy, or chlorine.

Compounds of formula I wherein both of X and Y are other than hydrogen.

Compounds of formula I wherein one of X and Y is other than hydrogen, fluorine, chlorine, methyl, hydroxy, cyano, carbamoyl, methylcarbamoyl, dimethylcarbamoyl or COOR₃₅, wherein R₃₅ is C₁₋₃ alkyl, C₂₋₅ haloalkyl, C₃₋₅ alkenyl, C₃₋₅ alkynyl, C₂₋₅ alkoxyalkyl, or benzyl optionally substituted by methyl, methoxy, methylthio, trifluoromethyl, halogen or nitro.

Combinations of these further preferred meanings with each other and with those set out above also deserve mention.

Examples of preferred compounds according to the invention are compound nos. 13, 40, 53, 55, 58, 64, 77, 78, 82, 91, 103, 108, 110, 111, 124, 125, 130, 143, 149, 163, 170, 175, 183, 199, 204, 205, 211, 219, 220, 224, 228, 247, 249, 258, 262, 263, 265, 266, 267, 272, 273, 277, 286, 294, 302, 310, 385, 403, 413, 452, 454, 455, 456, 457, 464, 473, 477, 479, 480, 481, 483, 487, 489, 504, 510, 522, 528, 531, 532, 539, 545, 547, 571, 576, 584, 590, 591, 593, 594, 595, 599, 605, 606, 607, 608, 612 and 622.

Compounds having the formula ##STR26## especially those wherein X is CN and at least one of W₁ and W₄ is nitrogen may exist in the alternate tautomeric form ##STR27##

The compounds of formula I according to the invention may be prepared as follows.

a) when X and R combine to form a bridging group as defined above and Y is hydrogen, cyano, arylthio, arylsulfinyl or arylsulfonyl, reacting a compound of formula II ##STR28## wherein A is as defined above, Y' represents hydrogen, cyano, arylthio, arylsulfinyl or arylfulfonyl and Z₁ represents oxygen, sulfur or NR₂ wherein R₂ is as defined above except for hydrogen, with a compound of formula III ##STR29## wherein W₁, W₂, W₃, W₄ are as defined above except that at least one of W₁ and W₄ is nitrogen and R₂₁ represents methylsulfonyl, or halogen to obtain the corresponding compound of formula Ip ##STR30## b) treating a compound of formula Ip wherein Y' represents cyano or arylsulfonyl and Z' represents oxygen and the other symbols are as defined above.

(i) by hydrolysis to give a corresponding compound of formula I wherein R and X form a bridge and Y is hydroxy or a compound of formula I wherein X and Y together form ═O

(ii) with an amine to give a corresponding compound of formula I wherein R is an optionally substituted carbamoyl group and X and Y together form ═O

(iii) with a group

    MOR.sub.22

wherein M is an alkali metal and R₂₂ is alkyl, to give a corresponding compound wherein R and X form a bridge and Y is alkoxy

c) hydrolyzing a compound of formula Ip wherein Y' represents hydrogen and Z₁ represents oxygen to give a compound of formula I wherein R is a carboxyl group optionally in salt form, X is hydrogen and Y is hydroxy

d) ring opening a compound of formula Ip wherein Y' represents hydroxy and Z₁ represents oxygen to give a compound of formula I wherein R is a carboxyl group optionally in salt form and X and Y together are ═O

e) esterifying a compound of formula I wherein R is a carboxyl group optionally in salt form and X and Y are ═O to give the corresponding compound wherein R is a carboxyl group in ester form

f) halogenating a compound of formula Ip wherein Y' represents hydroxy to give a compound of formula I wherein X and R together form a bridging group and Y' is halogen

g) reacting a compound of formula Ip wherein Z₁ is oxygen and Y' is halogen with a group R₂ NH₂ and a group HOR₂₃ wherein R₂₃ represents alkyl, acyl or aryl and R₂ is as defined above to give the corresponding compound wherein Z₁ is NR₂ and Y' is alkoxy, aryloxy or acyloxy

h) oxidizing a compound of formula Ip wherein Y' represents hydrogen to give the corresponding compound wherein Y' represents hydroxy

i) reacting a compound of formula IV ##STR31## with a compound of formula V ##STR32## to produce a compound of formula Iq ##STR33## wherein A, R, R₁, W₁, W₂, W₃, W₄, Y₁, Y₂ and Y₃ are as defined above and X" and Y" are hydrogen and R₂₄ is alkyl, especially methyl, cyanomethyl, alkoxycarbonylmethyl, carbamoylmethyl,

j) mono-or di-halogenating a compound of formula Iq wherein X" and Y" are hydrogen to produce the corresponding compound of formula Iq wherein one or both of X" and Y" are halogen

k) oxidizing a compound of formula Iq wherein X" and Y" are both hydrogen or X" is halogen and Y" is hydrogen to produce the corresponding compound wherein X" and Y" together represent ═O or one represents hydrogen and the other represents hydroxy

l) alkylating a compound of formula Iq wherein X" represents hydrogen and Y" represents hydrogen to produce the corresponding compound wherein X" represents alkyl and Y" represents hydrogen

m) introducing an alkoxy or alkylthio group into a compound of formula Iq wherein X" represents halogen and Y" represents hydrogen to produce the corresponding compound wherein X" represents alkoxy or alkylthio and Y" represents hydrogen

n) acylating a compound of formula Iq wherein X" represents hydroxy and Y represents hydrogen to produce the corresponding compound wherein X" represents acyloxy and Y" represents hydrogen

o) reacting a compound of formula Ip wherein Z₁ is oxygen and Y' is hydrogen with a group R₇ NH2 wherein R₇ is as defined above to give a compound of formula I wherein R is monosubstituted carbamoyl, X is hydrogen and Y is hydroxy

p) sulfonylating, carbamoylating, acylating or carbalkoxylating a compound of formula Ip wherein Z₁ is oxygen and Y' is hydroxy to produce the corresponding compound of formula Ip wherein Y' represents sulfonyloxy, carbamoyloxy, acyloxy or alkoxycarbonyloxy

q) reacting a compound of formula Ip wherein Z₁ is oxygen and Y' is halogen with a group R₇ R₈ NH wherein R₇ and R₈ are as defined above (R₇ and R₈ ≠H) to give a compound of formula I wherein R is disubstituted carbamoyl, and X and Y together represent ═O.

r) oxidizing a compound of formula ##STR34## to give a corresponding compound of formula I wherein X and Y together represent ═O.

s) reacting a compound of formula III with a compound of formula IV each as defined above to produce a compound of formula Iq wherein X" and Y" are hydrogen.

t) oxidizing a compound of formula I wherein X═Y═H to give a compound Ip wherein Z₁ is oxygen and Y' is hydroxy.

u) reacting a compound of formula V ##STR35## with a compound of formula IV wherein R is cyano and R₂₄ is halogen and oxidizing the product to give a compound of formula I where R is cyano and X and Y together represent ═O or of formula Ip wherein Z₁ represents ═O and y¹ is cyano.

and in each case recovering any compound wherein R is a carboxyl or thiocarboxyl group in free form or in ester form and any compound wherein R is carboxyl in free form or in salt form.

The following table is illustrative of suitable reaction conditions.

    __________________________________________________________________________     REACTION CONDITIONS                                                            Reaction Reagents   Solvents          Temperature                                                                            Others                           __________________________________________________________________________     a)                                                                               1) a) base eg LDA 1) and 2) inert eg DMF,                                                                          a) reduced eg -70°                  or b) base eg NaH ether, cyclic ether eg THF                                                                       b) R.T.                                    2) III            ∴                                                  b)                                                                               i)1) base eg NaOH inert eg ether,   R.T.                                                            cyclic ether eg THF or                                    2) acidity           alcohol eg methanol                                     b)                                                                               ii) 1) amine         inert eg ether, cyclic                                                         ether eg THF                                            b)                                                                               iii) MOR.sub.21   alcohol eg methanol,                                                              cyclic ether eg THF                                     c)                                                                               base eg LiOH         water optionally with an                                                       alcohol or cyclic ether eg THF                                                                   R.T.                                  d)                                                                               base eg NaOH         as c)             R.T.                                  e)                                                                               halide eg IR.sub.5                                                                                  inert eg DMF,     elevated eg                             base eg K.sub.2 CO.sub.3, NaH                                                                    2-butanone (MEK)  50-80°                            f)                                                                               halogenating         inert eg chlorinated                                                                             elevated eg                             agent eg SOCl.sub.2, DMF                                                                            hydrocarbon eg CCl.sub.4 CH.sub.2 Cl.sub.2                                                    40-80°                            g)                                                                               1) R.sub.7 NH.sub.22 ; R.sub.23 OH                                                               as f)             elevated eg                                                                       50-80°                         h)                                                                               1) oxidizing agent                                                                               1), 2) and 3) inert eg                                                                           elevated eg 50°                     eg NaOCl          H.sub.2 O optionally with alcoholo                           2) base eg NaOH      eg methanol       R.T.                                    3) acid eg HCl    cyclic ether eg THF                                                                                 R.T.                                  i)                                                                               1) base eg LDA       1) anhydr. inert eg ether such                                                                   reduced eg -30°                                       as cyclic ether eg THF                                    2) AcOH              2), 3) and 4) ether, H.sub.2 O                                                                   R.T.                                    3) DDQ                                 reduced eg 0°                    4) aq NaOH                          elevated eh 75°                   j)                                                                               NBS, benzoylperoxide                                                                                inert eh halogenated                                                                             elevated eg 75°                                       hydrocarbon such as CCl.sub.4                           k)                                                                               A. when X" = halogen and                                                       Y" = H to give X + Y are = O                                                   DMSO, Na.sub.2 CO.sub.3                                                                             DMSO              elevated eg 50-60°               B. when X- and Y" = H                                                          to give X" + Y" are = O                                                        a) SeO.sub.2         AcOH              110°, 1 hr; or                   b) t-butylhydro-     CH.sub.3 CN       85°; or                          peroxide                                                                       Co.sub.2 (CO).sub.8                                                            c) 1) Mn(OAc).sub.3                                                                                 AcOH              25 → 100°                 2) H.sub.2 O                                                                   C. when X" and Y" = H                                                          to give X" = OH, Y" = H                                                        i) nBuLi             THF               -78°                             ii) t-butyl peroxy-                                                                                 THF               -78° → 20°         benzoate                                                                       iii) BF.sub.3.MeOH                                                                                  toluene           40° → 100°       l)                                                                               base eg NaH, alkyl                                                                               inert eg ether, THF                                                                              0° → R.T.                    halide                                                                       m)                                                                               MOR.sub.22, MSR.sub.22                                                                              inert eg DMF, alcohol                                                                            R.T. → 50°                eg NaOCH.sub.3                                                                      O                                                                       n)                                                                               acyl chloride eg CH.sub.3 CCl                                                                       inert eg ether, THF                                                                              R.T. → 30°                or anhydride eg Ac.sub.2 O;                                                                         pyridine                                                  amine eg triethylamine                                                       o)                                                                               amine, eg α-methyl                                                                         alcohol eg methanol                                                                              R.T. → 80°                   benzylamine                                                                      or                                                                           amine, eg aniline,                                                                                  inert eg toluene                                                                                 R.T.                                    CH.sub.3 SO.sub.2 NH.sub.2 ; Me.sub.3 Al (catalyst)                                                 CH.sub.2 Cl.sub.2                                       p)                                                                               acylchloride eg acetyl-                                                                             inert eg ether    R.T.                                    chloride, ethylchloro- THF, puridine                                           formate or anhyydride; amine                                                   eg DMAP, triethylamine                                                           or                                                                           isocyanate eg methylisocyanate;                                                                      ∴        ∴                               amine eg triethylamine                                                           or                                                                           sulfonyl chloride eg methyl                                                                          ∴     ∴                                  sulfonyl chloride; amine eg                                                    triethylamine                                                                q)                                                                               R.sub.7 R.sub.8 NH, triethylamine,                                                                  inert eg CH.sub.2 Cl.sub.2                                                                       ∴                               DMAP                                                                         r)                                                                               i) m-chlorobenzoic acid                                                                             inert eg CH.sub.2 Cl.sub.2                                                                       20°, 30 min                      ii) base eg NaOH     inert eh cyclic ether                                                                            20°, 30 min                    s)                                                                               1) LDA               THF               -78°                             2) III               THF               -78° → 20°       t)                                                                               KMnO.sub.4           H.sub.2 O         100° C.                        u)                                                                               i) base eg K.sub.2 CO.sub.3, KOBu.sup.t,                                                            inert eg DMF, THF                                                                                RT → 100° C.              NaH                                                                            ii) oxidizing agent eh NaOCl                                                                        water optionally with inert                                                                      RT                                      or H.sub.2 O.sub.2 /AcOH                                                                            eg cyclic ether or CH.sub.3 CM                          __________________________________________________________________________

Processes a) through u) also form part of the invention.

The starting materials of formula II or III are either known or may be prepared analogously to known methods.

The compounds of formula I have herbicidal activity as observed after their pre-emergent or post-emergent application to weeds or a weed locus.

The term "herbicide" (or "herbicidal") refers to an active ingredient (or an effect) which modifies the growth of plants because of plant growth regulating or phytotoxic properties so as to retard the growth of the plant or damage the plant sufficiently to kill it.

Application of a compound of formula I is made according to conventional procedure to the weeds or their locus using a herbicidally effective amount of the compound, usually from 10 g to 10 kg/ha.

Compounds according to the invention may be used in the control of both broad-leaf and grassy weeds on both pre- and post-emergent application. Compounds may also exhibit selectivity in various crops and are thus suited for use in weed control in crops such as corn, cotton, wheat, soybean and rice.

The optimum usage of a compound of formula I is readily determined by one of ordinary skill in the art using routine testing such as greenhouse testing and small plot testing. It will depend on the compound employed, the desired effect (a phytotoxic effect requiring a higher rate than a plant growth regulating effect), the conditions of treatment and the like. In general satisfactory phytotoxic effects are obtained when the compound of formula I is applied at a rate in the range of from 0.01 to 5.0 kg, more preferably of from 0.05 to 2.5 kg per hectare, eg 0.05 to 5.0 kg per hectare, especially 0.1 to 2.5 kg per hectare.

The compounds of formula I may be advantageously combined with other herbicides for broadspectrum weed control. Examples of herbicides which can be combined with a compound of the present invention include those selected from the carbamates, thiocarbamates, chloroacetamides, dinitroanilines, benzoic acids, glycerol ethers, pyridazinones, semicarbazones, uracils and ureas for controlling a broad spectrum of weeds.

The compounds of formula I are conveniently employed as herbicidal compositions in association with agriculturally acceptable diluents. Such compositions also form part of the present invention. They may contain, aside from a compound of formula I as active agent, other active agents, such as herbicides or compounds having antidotal, fungicidal, insecticidal or insect attractant activity. They may be employed in either solid or liquid forms eg in the form of a wettable powder or an emulsifiable concentrate incorporating conventional diluents. Such compositions may be produced in conventional manner, eg by mixing the active ingredient with a diluent and optionally other formulating ingredients such as surfactants.

Agriculturally acceptable additives may be employed in herbicidal compositions to improve the performance of the active ingredient and to reduce foaming, caking and corrosion, for example.

The term "diluent" as used herein means any liquid or solid agriculturally acceptable material which may be added to the active constituent to bring it in an easier or improved applicable form, respectively, to a usable or desirable strength of activity. It can for example be talc, kaolin, diatomaceous earth, xylene or water.

"Surfactant" as used herein means an agriculturally acceptable material which imparts emulsifiability, spreading, wetting, dispersibility or other surface-modifying properties. Examples of surfactants are sodium lignin sulfonate and lauryl sulfate.

Particularly formulations to be applied in spraying forms such as water dispersible concentrates or wettable powders may contain surfactants such as wetting and dispersing agents, for example the condensation product of formaldehyde with naphthylene sulphonate, an ethoxylated alkylphenol and an ethoxylated fatty alcohol.

In general, the formulations include from 0.01 to 90% by weight of active agent and from 0 to 20% by weight of agriculturally acceptable surfactant, the active agent consisting either of at least one compound of formula I or mixtures thereof with other active agents. Concentrate forms of compositions generally contain between about 2 and 90%, preferably between about 5 and 70% by weight of active agent. Application forms of formulation may for example contain from 0.01 to 20% by weight of active agent.

Typical herbicidal compositions, according to this invention, are illustrated by the following Examples A, B and C in which the quantities are in parts by weight.

EXAMPLE A

Preparation of a Dust

10 Parts of a compound according to this invention and 90 parts of powdered talc are mixed in a mechanical grinder-blender and are ground until a homogeneous, free-flowing dust of the desired particle size is obtained. This dust is suitable for direct application to the site of the weed infestation.

EXAMPLE B

Preparation of a Wettable Powder

25 Parts of a compound according to this invention are mixed and milled with 25 parts of synthetic fine silica, 2 parts of sodium lauryl sulphate, 3 parts of sodium ligninsulphonate and 45 parts of finely divided kaolin until the mean particle size is about 5 micron. The resulting wettable powder is diluted with water before use to a spray liquor with the desired concentration.

EXAMPLE C

Preparation of Emulsifiable Concentrate (EC)

13.37 Parts of a compound according to this invention are mixed in a beaker with 1.43 parts of Toximul 360A (a mixture of anionic and non-ionic surfactants containing largely anionic surfactants), 5.61 parts of Toximul 360A (a mixture of anionic and non-ionic surfactants containing largely non-ionic surfactants), 23.79 parts of dimethylformamide and 55.8 parts of Tenneco 500-100 (predominantly a mixture of alkylated aromatics such as xylene and ethylbenzene) until solution is effected. The resulting EC is diluted with water for use.

The following examples are provided to illustrate the practice of the present invention. Temperature is given in degrees Celsius. Abbreviations used in this specification.

THF=tetrahydrofuran

LDA=lithium diisopropylamide

RT=room temperature

DMF=dimethylformamide

DDQ=2,3-dichloro-5,6-dicyanobenzoquinone

NBS=N-bromosuccinimide

DMSO=Dimethylsulfoxide

MEK=Methylethylketone

DMAP=4-Dimethylaminopyridine

Individual alkyl substituents listed in the following tables from A to F are in the "n" isomeric form unless otherwise indicated.

EXAMPLE 1 7-chloro-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide (Table A, cpd. no. 6)

1.68 g (0.01 mol) of 7-chlorophthalide is added to 100 ml of dry THF and the mixture cooled to -70° C. 6.8 ml (0.01 mol) of 1.5M LDA is then added over 3 minutes and the reaction mixture stirred at -70° C. for 15 minutes. 2.18 g (0.01 mol) of 2-methylsulfonyl-4,6-dimethoxypyrimidine in 50 ml of THF is then added and the mixture stirred for 4 hrs with temperature being maintained at -75° to -70° C. The reaction mixture is neutralized with 1.5 g of NH₄ Cl in 5 ml of water, warmed and concentrated on a rotovaporator. The concentrate is partitioned between CH₂ Cl₂ /H₂ O (50 ml each) and the aqueous phase separated and treated with further 30 ml of CH₂ Cl₂. The combined CH₂ Cl₂ phases are washed with 30 ml of water, separated and concentrated. The concentrate was flash chromatographed on silica gel using 80/20 hexane/ethyl acetate (500 ml), 50/50 hexane/ethyl acetate (500 ml) and 80/20 acetone/methanol (500 ml) (30 fractions×50 ml). The title compound (fractions 9-23) was obtained after recrystallization from hexane/CH₂ Cl₂ as a white solid, m.p. 148°-149° C.

EXAMPLE 2 5-(4,6-dimethoxy-2-pyrimidinyl)-furo[3,4-b] pyridine-7(5H)-one (Table B, cpd. no. 40)

A solution of 1.3 g (0.0096 mols) of furo[3,4-b]pyridine-7(5H)-one in 50 ml of dry THF is cooled to -75° C. and 8 ml (0.0192 mols) of 2.5M LDA added dropwise over 5 minutes. The mixture is allowed to react for 1 hr at -75° C. and 2.1 g (0.0096 mol) of 2-methylsulfonyl-4,6-dimethoxypyrimidine in 30 ml of dry THF added dropwise over 10 minutes. The mixture is allowed to warm to RT, 1.6 ml of HCl added and the THF evaporated off. The residue is dissolved in 75 ml of CH₂ Cl₂, washed with water (2×50 ml) and the organic phase concentrated to give a yellowish white gummy solid. This is chromatographed on a silica gel column using 50/50 hexane/ethyl acetate (500 ml), ethyl acetate (500 ml) and 80/20 acetone/methanol (1000 ml) (30 fractions). The crystalline residue (fractions 18-21) of the title product has m.p. of 167-168° C.

EXAMPLE 3 7-chloro-3-methoxy-3-(4,6-dimethoxy-2-pyrimidinyl)-2-methyl-isoindol-1(3H)-one (Table C, cpd. no. 54)

A mixture of 0.5 g of 7-chloro-3-hydroxy-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide, 30 ml of CCl₄, 2 ml of SOCl₂ and 4 drops of DMF is heated at 65° C. for 11/2 hrs, cooled and excess SOCl₂ and CCl₄ removed on a rotovaporator. The residue is diluted with 20 ml of CH₂ Cl₂ and added to a mixture of 5 ml of 40% aq methylamine and 10 ml of methanol with stirring over 1/2 hr. The mixture is placed on a rotovaporator and the residue partitioned between 50 ml each of CH₂ Cl₂ and water. The organic phase is concentrated and flash chromatographed on silica gel using 50/50 hexane/ethyl acetate (800 ml), ethyl acetate (500 ml) and 80/20 acetone/methanol (200 ml) (30 fractions ×50 ml). The product (fractions 19-21) was obtained as a yellow gum.

EXAMPLE 4 7-chloro-3-hydroxy-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide (Table A, cpd. no. 13)

A mixture of 1.8 g of 7-chloro-3-cyano-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide, 50 ml of 1% NaOH and 50 ml of THF are stirred at room temperature for 3 hrs. The THF is removed by evaporation and the mixture is diluted with water and extracted twice with ethyl acetate. The aqueous solution is acidified with 2N--H₂ SO₄. The resulting acid solution is extracted with 3×100 ml ethyl acetate and the organic phases combined, dried over Na₂ SO₄ and concentrated to give a pale yellow solid. This residue is taken up in ethyl acetate and treated with activated charcoal until the yellow base line material is removed to give the title product as a white solid m.p. 188°-190° C.

EXAMPLE 5 7-chloro-3-methoxy-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide (Table A, cpd. no. 30)

1.0 g of 7-chloro-3-cyano-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide is slurried in 20 ml of methanol and the solution cooled with ice and 0.6 ml of sodium methoxide added dropwise. After stirring for 10 min a further 1 ml of sodium methoxide is added and stirring continued for 10 min and the mixture is then quenched with 2N H₂ SO₄. Methanol is removed on a rotovaporator and the residue partitioned between water and ethyl acetate. The organic phase is dried over Na₂ SO₄ and concentrated. Flash chromatography of the residue over silica gel using 25% ethyl acetate/hexane yields a white solid m.p. 180°14 183° C.

EXAMPLE 6

a) Methyl 2-chloro-6-(4,6-dimethoxy-2-pyrimidinylcarbonyl)benzoate (Table C, cpd. no. 55), and

b) 7-chloro-3-chloro-(4,6-dimethoxy-2-pyrimidinyl)phthalide (Table A, cpd. no. 21)

A mixture of 0.7 g of 7-chloro-3-hydroxy-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide, 30 ml of CCl₄, 2 ml of SOCl₂ and 4 drops of DMF are refluxed at 60° for 11/2 hrs. The mixture is then cooled, excess SOCl₂ and CCl₄ removed on a rotovaporator. The residue is diluted with 20 ml of CH₂ Cl₂ and added to a stirred mixture of 10 ml of methanol and 2 ml of diethylamine. After 21/2 hrs the mixture is stripped on a rotovaporator to remove excess CH₂ Cl₂ and methanol and the residue partitioned between CH₂ Cl₂ (50 ml) and water (50 ml). The organic phase is separated, concentrated and the gummy residue flash chromatographed over silica gel using 80/20 hexane/ethyl acetate (500 ml), 60/40 hexane/ethyl acetate (500 ml) (28 fractions×50 ml). Fractions 18 to 20 yielded title compound a) and fractions 11 to 16 the compound b).

EXAMPLE 7 7-chloro-3-cyano-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide (Table A, cpd. no. 27)

600 mg of 7-chloro-3-cyanophthalide are added to an ice-cold suspension of hexane washed 60% NaH (160 mg) in DMF (20 ml). After 15 min, 710 mg of 2-methylsulfonyl-4,6-dimethoxypyrimidine are added. After stirring at RT for 11/2 hr the mixture is poured onto 200 ml of ice/water acidified with 2N H₂ SO₄ and stirred. The precipitate is filtered and dried in a vacuum oven to yield the title product, m.p. 159°-161° C.

EXAMPLE 8 7-chloro-3,3-bis(4,6-dimethoxy-1,3,5-triazin-2-yl)phthalide (Table A, cpd. no. 36)

1.48 g of 7-chlorophthalide are dissolved in 80 ml of THF. The solution is cooled to -70° C. and 1.5M LDA in THF (6 ml) is syringed in at -70° C. over 3 min. Stirring is continued for 15 min at -70°, 1.54 g of 2-chloro-4,6-dimethoxy-1,3,5-triazine in 50 ml of THF added dropwise and the mixture is then allowed to warm to -20°. The mixture is again cooled to -70° and 1 ml of conc. HCl in 10 ml of water is added. The mixture is stirred for 25 min and allowed to warm to RT and the THF is removed by evaporation. The residue is partitioned between CH₂ Cl₂ and water (50 ml each) and the aqueous phase extracted with an additional 30 ml of CH₂ Cl₂. The combined organic phases are washed with 30 ml of water and concentrated to give a yellow gum. This is flash chromatographed on silica gel using 60/40 hexane/ethyl acetate (1000 ml), ethyl acetate (400 ml), 80/20 acetone/methanol (500 ml) (30 fractions×50 ml, 1×200 ml). Fractions 21 and 22 yielded a yellow gum which upon recrystallization from hexane yielded title product m.p. 126°-127° as a yellow solid.

EXAMPLE 9

Lithium 2-chloro-6-(4,6-dimethoxy-α-hydroxy-2-pyrimidinylmethyl)benzoate (Table C, cpd. no. 53)

A mixture of 1.0 g of 7-chloro-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide, 0.136 g of LiOH.H₂ O, 2 ml of water and 10 ml of methanol is stirred overnight at RT. The mixture is evaporated to dryness on a rotovaporator. Further drying in a drying pistol yield the title compound as a white solid, m.p. 153°-157° C.

EXAMPLE 10 Lithium 3-[(4,6-dimethoxy-α-hydroxy-2-pyrimidinyl)methyl]pyridine-2-carboxylate (Table E, cpd. no. 64)

A mixture of 0.490 g of 5-(4,6-dimethoxy-2-pyrimidinyl)furo[3,4,b]-pyridine7(5H)-one, 0.0768 gm of LiOH.H₂ O, 10 ml of methanol and 2 ml of water is stirred for 24 hrs under nitrogen at RT and the solvent stripped off. The yellowish solid is dried for a further 2 hrs to yield the title product, m.p. >250° C. (decomp.).

EXAMPLE 11 Sodium 2-chloro-6-[(4,6-dimethoxy-2-pyrimidinyl)carbonyl]benzoate (Table C, cpd. no. 58)

1.24 g of 7-chloro-3-hydroxy-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide, 154 mg NaOH, 25 ml THF and 25 ml water are mixed until a yellow homogenous solution is achieved. The solvents are stripped on a rotovaporator and then on a Kugelrohr at 100° C. to produce the title compound as a yellow solid, m.p. 276°-278° C.

EXAMPLE 12 3-[(4,6-dimethoxy-2-pyrimidinyl)carbonyl]-pyridine-2-carboxylic acid (Table E, cpd. no. 63)

490 mg of 5-(4,6-dimethoxy-2-pyrimidinyl)-furo[3,4-b]pyridine-7(5H)-one is dissolved in 50 ml of methanol and the mixture heated with stirring at 50° C. until a homogenous solution is formed (ca 1/2 hr). 2.6 g of NaOCl is added dropwise and the solution heated for a further 1/2 hr at 55° C. 0.208 g of 50% NaOH is added at 55° and the mixture heated for a further 1/2 hr at this temperature and then cooled in an ice-bath and acidified with 1 ml conc. HCl The solvent is evaporated and the residue partitioned between 50 ml of CH₂ Cl₂ and 50 ml of water. The organic phase is concentrated to give a white solid, m.p. 71°-73°.

EXAMPLE 13 2-[(4,6-dimethoxy-2-pyrimidinyl)-α-iminomethyl]benzoic acid (Table C, cpd. no. 51)

2.67 g of isopropyl 2-bromobenzoate are dissolved in 100 ml of dry diethylether, the solution cooled to -100° C. and 6.6 ml of 1.6M n-butyl-lithium solution added. Stirring is continued for 10 min and 12 g of 2-cyano-4,6-dimethoxypyrimidine in 60 ml of diethylether is added over 2 min at -100° C. The mixture is stirred for 1/2 hr at -80° and then allowed to warm to RT. 3 g of NH₄ Cl in 30 ml of water is added to the reaction mixture, cooled in an ice-bath. The ether layer is separated off, washed with water (2×30 ml) and concentrated. The gummy residue is dissolved in 20 ml of 85/15 hexane/ethyl acetate, and CH₂ Cl₂, and flash chromatographed on silica gel using 800 ml 85/15 hexane/ethyl acetate, 500 ml 1% methanol in ethyl acetate, 500 ml 5% methanol in ethyl acetate and 500 ml of 80/20 acetone/methanol (40 fractions at 50 ml; 1 at 200 ml). Fractions 7 to 10 yielded title compound which on recrystallization from CH₂ Cl₂ melted at 225°-235° C.

EXAMPLE 14 5-Chloro-5-(4,6-dimethoxy-2-pyrimidinyl)furo[3,4-b]pyridine-7(5H)-one (Table B, cpd. no. 68)

A mixture of 490 mg of 5-(4,6-dimethoxy-2-pyrimidinyl)furo[3,4,b]-pyridine-7(5H)one and 50 ml of methanol is heated at 55° for 1/2 hour or until a homogenous solution is formed. 2.6 g of NaOCl (common house bleach) is added dropwise. The mixture is taken up in dichloromethane an the organic phase separated and evaporated to dryness to yield the title compound, mp 146°-148° C.

EXAMPLE 15 3-[(4,6-dimethoxy-2-pyrimidinyl)carbonyl]-pyridine-2-carboxylic acid (Table E, cpd. no. 63)

0.208 g of 50% NaOH is added at 55° to a solution of 0.551 g of 5-chloro-5-(4,6- dimethoxy-2-pyrimidinyl )-furo[3,4,b]pyridine (Table B, cpd. no. 68) in 50 ml methanol. The mixture stirred for a further 1/2 hr at 55°, cooled in an ice-bath, acidified with 1 ml of concentrated HCl and the solvent evaporated. The residue is partitioned between 50 ml of CH₂ Cl₂ and 50 ml H₂ O and the CH₂ Cl₂ layer concentrated to give 0.39 g of the title product as a white solid, m.p. 71°-73° C.

EXAMPLE 16 2-(2-(4,4-dimethyl-oxazolin-2-yl)-benzyl)-4,6-dichloropyrimidine (Table C, cpd. no. 61)

To a mixture of 1.25 g of 2-o-tolyl-4,4-dimethyl-oxazoline in 20 ml of ether under N₂ atmosphere at -30° C. is added by syringe 4.2 ml of 1.6M n-butyllithium in hexane with stirring which is continued for 1 hr at -10° C. 0.98 g of 4,6-dichloropyrimidine in 20 ml of ether are added slowly to the reaction mixture which is then stirred at -45° to -30° C. for 30 min and at 0° C. for a further 30 min. The reaction mixture is quenched with acetic acid (0.4 ml) and water (0.1 ml) in THF (1.3 ml) and then treated with 1.5 g of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in 6 ml of THF. The temperature is brought to RT and the mixture stirred for 5 min after cooling to 0° C. 7.6 ml of 1N NaOH (cooled) are added and the mixture stirred for 5 min. The organic phase is separated and dried over Na₂ SO₄ filtered and the solvent removed. Following chromatography (10/90 ether/hexane) the title product is obtained.

EXAMPLE 17 2-(2-(4,4-dimethyl-oxazolin-2-yl)-benzyl)-4,6-dimethoxypyrimidine (Table C, cpd. no. 48)

To a solution of 1.7 g of 2(2-(4,4-dimethyl-oxazolin-2-yl)-benzyl)-4,6-dichloropyrimidine in 100 ml of methanol are added 2.18 g of 25% methanolic NaOCH₃ and the mixture heated for 10 hrs at 65° C. with stirring. The temperature is lowered to 60° and stirring continued overnight. The solvent is stripped and the residue taken up in 80 ml of toluene and 50 ml of water. The toluene layer was separated and washed with 50 ml of water, separated and concentrated to give the title compound as a yellow oil.

EXAMPLE 18 2-(2-(4,4-dimethyl-oxazolin-2-yl)-α-bromobenzyl)-4,6-dimethoxy pyrimidine (Table C, cpd. no. 62)

0.55 g of 2-(2-(4,4-dimethyl-oxazolin-2-yl)-benzyl)-4,6-dimethoxypyrimidine, 0.30 g of a N-bromosuccinimide, 0.03 g of benzoyl peroxide are dissolved in 60 ml of CCl₄ and heated under reflux overnight at 75° C. The reaction mixture is filtered and the filtrate washed with 5% NaHCO₃ solution (50 ml), 50 ml of water and the organic phase separated and concentrated to give the title compound.

EXAMPLE 19 2-(2-(4,4-dimethyl-oxazolin-2-yl)-benzoyl)4,6-dimethoxypyrimidine (Table C, cpd. no. 49)

A mixture of 1.2 g of 2-(2-(4,4-dimethyl-oxazolin-2-yl)-α-bromobenzyl)-4,6-dimethoxy-pyrimidine and 2 g of Na₂ CO₃ in 30 ml of DMSO is heated with stirring at 50°-60° C. for 3 hrs. The mixture is poured into 150 ml of water and extracted with toluene. The toluene extract is washed twice with water (2×50 ml) separated and concentrated. The thus obtained gum is chromatographed with 800 ml of 80/20 hexane/ethyl acetate, 500 ml 70/30 hexane/ethyl acetate, 60/40 ml hexane/ethyl acetate (50 ml fractions) fractions 29 to 34 yielded the title compound.

EXAMPLE 20 2-chloro-6-(4,6-dimethoxy-2-pyrimidinylcarbonyl)-benzoic acid dimethylamide (Table C, cpd. no. 57)

1.0 g of 7-chloro-3-cyano-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide is dissolved in 15 ml of THF. 0.7 ml of a 40% aqueous dimethylamine solution is then added via syringe whereupon the solution darkens. Stirring is continued at R.T. for 15 minutes and the mixture diluted with water and partitioned between ethyl acetate and water. The organic phase is separated, washed with 2N H₂ SO₄, then brine, dried and concentrated. The residue is purified on silica gel, eluant 200 ml of 50% ethyl acetate/hexane then 100% ethyl acetate. Fractions 12 to 15 yielded the title compound, m.p. 141°-142° C.

EXAMPLE 21 3-acetoxy-7-chloro-3-(4,6-dimethyloxy-2-pyrimidinyl)phthalide (Table A, cpd. no. 125)

1.1 g of 7-chloro-3-(4,6-dimethoxy-2-pyrimidinyl)-3-hydroxy-phthalide is dissolved in 20 ml of pyridine and 0.3 ml of acetic anhydride added with stirring. After stirring for 20 min the mixture is poured into 2N HCl and extracted with two portions of ethyl acetate. The combined ethyl acetate extracts are washed once with 2N HCl, once with H₂ O and once with brine and dried over magnesium sulfate. Filtration and evaporation produced the title compound as a white solid, m.p. 213°-215°.

EXAMPLE 22 3-[(4,6-dimethoxy-α-hydroxy-2-pyrimidinyl)methyl]pyridine-2-carboxamide (Table E, cpd. no. 82)

To a solution of 0.9 g of ammonia, in 15 ml of methanol, is added 0.5 g of 3[(4,6-dimethoxy-2-pyrimidinyl)-7-azaphthalide. After stirring for 2 hrs at RT, the methanol is removed under reduced pressure and the concentrate recrystallized from toluene to give the title compound as a white solid, m.p. 135°-137° C.

EXAMPLE 23 3[(4,6-dimethoxy-2-hydroxy-2-pyrimidinyl)methyl]pyridine-2-[carboxy-(4-isopropyl)anilide] (Table E, cpd. no. 183)

To a solution of 3 ml of 4-isopropylaniline in 50 ml of toluene is syringed in 4 ml of 15.6% trimethylaluminum in hexane at RT. The mixture is stirred for 0.5 hr at RT and 0.5 g of 3-[(4,6-dimethoxy-2-pyrimidinyl)-7-azaphthalide is added. The mixture is stirred for 2 hrs at RT and acidified with 30 ml of 10% hydrochloric acid at 5°-10° C. The toluene solution is separated, washed with 20 ml of 10% hydrochloric acid, 20 ml of 5% sodium carbonate and 20 ml of water, dried and concentrated. The concentrate is recrystallized from hexane to yield the title compound as a white solid, m.p. 113°-114° C.

EXAMPLE 24 3-[(4,6-dimethoxy-α-(ethoxycarbonyloxy)-2-pyrimidinyl)methyl]-pyridine-2-carboxamide (Table E, cpd. no. 129)

To a solution of 0.5 g of 3-[(4,6-dimethoxy-α-hydroxy-2-pyrimidinyl)methyl]pyridine-2-carboxamide, 0.05 g of 4-(dimethylamino)pyridine, and 1 ml of triethylamine, in 20 ml of toluene and 10 ml of dichloromethane is added 1 ml of ethyl chloroformate at RT. After stirring for 1 hr at ambient temperature, the mixture is washed with water (2×30 ml), dried and concentrated on a rotoevaporator. The concentrate is digested with 1/1 mixture of hexane-toluene, 10 ml, at 50° C., cooled to RT and filtered to isolate 0.45 g of the title compound as a yellow solid, m.p. 112°-114° C.

EXAMPLE 25 3-[(4,6-dimethoxy-α-benzoyloxy-2-pyrimidinyl)methyl]pyridine-2-(N,N-dibenzoyl)carboxamide (Table E, cpd. no. 159)

To a solution of 0.05 g of 3-[(4,6-dimethoxy-α-hydroxy-2-pyrimidinyl)methyl]-2-carboxamide, 0.5 g, 4-(dimethylamino)pyridine and 4 ml of triethylamine in 30 ml of dichloromethane is added 1.4 g of benzoyl chloride at RT in two portions. The reaction mixture is stirred at RT for 17 hrs and washed with 30 ml of water, 30 ml of 5% hydrochloric acid and 30 ml of water. The dichloromethane solution is concentrated and the concentrate flash chromatographed through 300 ml silica gel, 230-400 mesh, using 1 L 70/30 hexane-ethyl acetic and 500 ml 50/50 hexane-ethyl acetate as eluting solvent mixtures. Fractions 18-21 gave after recrystallization from 70/30 hexane ethyl acetate the title compound as a white solid, m.p. 168°-170° C.

EXAMPLE 26 3-[(4,6-dimethoxy-α-(N-methylcarbamoyloxy)-2-pyrimidinyl)methyl]-2-pyridine carbox(N-allyl)amide (Table E, cpd. no. 133)

To a solution of 0.5 g of 3-[(4,6-dimethoxy-α-hydroxy-2-pyrimidinyl)methyl]-2-pyridine carbox(N-allyl)amide and 3 drops of triethylamine, in 20 ml of dichloromethane is added 3 ml of methyl isocyante, in three 1 ml portion/day while stirring at RT for 3 days. The reaction mixture is washed with water (2×50ml), dried and concentrated. The concentrate is flash chromatographed through 300 ml silica gel, 230-400 mesh, using 1 L 50/50 hexane-ethyl acetate, 500 ml ethyl acetate, 500 ml 80/20 ethyl acetate methanol taking 34 fractions (50 m/m). Fractions 21-25 give 0.4 g of the title product as a yellow gum.

EXAMPLE 27 Preparation of ethyl 2-bromo-4-[(4,6-dimethoxy-2-pyrimidinyl)methyl]nicotinate (Table D, cpd. no. 523)

7.32 g of ethyl 2-bromo-4-methyl nicotinate and 150 ml of THF are cooled in a dry ice/acetone bath under N₂ atmosphere, 30 ml of LDA are added over 5 mins and the mixture stirred for 30 mins. 6.55 g of 2-methylsulphonyl-4,6-dimethoxypyrimidine are added as a solid, rinsing with 50 ml of THF, and the mixture stirred cold for 2 hrs and slowly allowed to warm. The THF is evaporated, ca 75 ml of water added and the mixture extracted three times with methylene dichloride. The combined extracts are evaporated and the residue taken up with 20 ml of 25% ethyl acetate/hexane and flash chromatographed using 2 l of 25% ethyl acetate/hexane in 50 ml fractions. Fractions 7 to 14 are combined, evaporated and placed in a Kugelrohr at ca 105° for 2 hrs. The residue is taken up in 20 ml of 10% ethyl acetate/hexane and flash chromatographed with 2 l 10% ethyl acetate/hexane in 50 ml portions to yield title compound (NMR) in fractions 18 to 32.

EXAMPLE 28 Preparation of ethyl 2-bromo-4-[(4,6-dimethoxy-2-pyrimidinyl)carbonyl]nicotinate (Table D, cpd. no. 524)

3.28 g of ethyl 2-bromo-4-[(4,6-dimethoxy-2-pyrimidinyl)methyl]nicotinate, 3.61 g of SeO₂ and 100 ml of glacial acetic acid are combined under nitrogen, heated to 110° for 1.5 hrs and slowly cooled to RT still under nitrogen. The mixture is filtered, washed through with 10 ml of acetic acid and the filtrate evaporated to remove the acetic acid. 100 ml of methylene dichloride is added to the residue and the mixture washed twice with 100 ml of sat. aqueous NaHCO₃. The CH₂ Cl₂ phase is filtered and evaporated and the residue digested with 25 ml of 25% ethyl acetate/hexane at 50° for 15 mins. This solution is then poured onto a silica gel column and eluted with 3×125 ml of 25% ethyl acetate/hexane. Evaporation of combined fractions 1 and 2 yields the title product mp 98°-99°.

EXAMPLE 29 Preparation of 1-(4,6-dimethoxy-2-pyrimidinyl)-1-hydroxy-4-methyl-furo[3,4-c]pyridine-3(1H)-one (Table B, cpd. no. 260)

0.37 g of ethyl 2-methyl-4-[4,6-dimethoxy-2-pyrimidinyl)methyl]nicotinate, 0.37 g of potassium permanganate and 100 ml of water are combined and heated at reflux for 45 mins. The mixture is cooled, a further 0.185 g of permanganate added and refluxing resumed for 45 mins. The mixture is cooled to RT, filtered through celite, and sodium sulfite added until the aqueous layer becomes colorless. The filtrate is once again filtered, washed with water and extracted with 4×75 ml of methylene chloride. The combined extracts are evaporated, the residue taken up in 50 ml of warm ethyl acetate and poured onto a silica column and eluted with 2×100 ml of ethyl acetate. The combined fractions are evaporated to yield title product mp 203°-204°.

EXAMPLE 30 Preparation of N-methyl 3-phenyl-5-(4,6-dimethoxy-2-pyrimidinyl-α-t-butoxymethyl)-4-isoxazolecarboxanilide (Table F, cpd. no. 412)

To a solution of 1.29 g of N-methyl 3-phenyl-5-(4,6-dimethoxy-2-pyrimidinylmethyl)-4-isoxazolecarboxanilide, in 60 ml of THF is syringed in 2 ml of 1.5 molar n-butyl lithium in hexane at -70° C. The mixture is stirred for 10 mins at -70° C. and 0.6 g of t-butylperoxybenzoate, in 10 ml of THF, added over 10 mins. The reaction mixture is stirred at -70° C. for 1 hr and allowed to warm to RT. The mixture is diluted with 300 ml of water and extracted with 2×30 ml of toluene. The toluene solution is dried, concentrated and the concentrate flash chromatographed through 300 ml of silica gel, 230-400 mesh, using 1 l of 70/30 hexane/ethyl acetate, 500 ml of 50/50 hexane/ethyl acetate taking 30×50 ml fractions. Fractions 11-14 give the title compound as a yellow gum.

EXAMPLE 31 Preparation of N-methyl 3-phenyl-5-(4,6-dimethoxy-2-pyrimidinyl-α-hydroxymethyl)-4-isoxazolecarboxanilide (Table F, cpd. no. 424)

A mixture of 0.6 g of N-methyl 3-phenyl-5-(4,6-dimethoxy-2-pyrimidinyl-α-t-butoxymethyl)-4-isoxazolecarboxanilide, and 4 drops of borontrifluoridemethanol complex in 50 ml of toluene is heated at 50°-55° C. for 2 hours, washed with 20 ml of water, 50 ml of 5% sodium bicarbonate solution, dried and concentrated. The concentrate is recrystallized from hexane/methylene dichloride to give a white solid, mp 130°-131° C.

EXAMPLE 32 Preparation of N-methyl 3-phenyl-5-(4,6-dimethoxy-2-pyrimidinylcarbonyl)-4-isoxazolecarboxanilide (Table F, cpd. no. 429)

To a solution of 1.5 ml of oxalyl chloride in 30 ml of methylenedichloride cooled to -60° C. is added a solution of 2 ml of DMSO in 10 ml of methylene dichloride dropwise at -60° C. After 2 mins. a solution of 0.6 g of N-methyl 3-phenyl-5-(4,6-dimethoxy-2-pyrimidinyl-α-hydroxymethyl)-4-isoxazolecarboxanilide in 10 ml of methylene dichloride is added over 3 mins at -60° C. The mixture is stirred for 15 mins at -60° C. and 1 ml of triethylamine added. The mixture is allowed to warm to RT, washed with water (3×30ml), dried and concentrated. The concentrate is flash chromatographed through 300 ml silica gel, 230-400 mesh, using 1 l 60/40 hexane/ethyl acetate, 500 ml 50/50 hexane/ethyl acetate taking 25×50 ml fractions. Fractions 11-14 give the desired product, a yellow gum.

EXAMPLE 33 Preparation of N-methyl 3-phenyl-5-(4,6-dimethoxy-2-pyrimidinylcarbonyl)-4-isoxazolecarboxanilide (Table F, cpd. no. 429, alternative method)

A solution of 100 mg of N-methyl 3-phenyl-5-(4,6-dimethoxy-2-pyrimidinylmethyl)-4-isoxazolecarboxanilide, 20 mg of dicobalt octacarbonyl, and 1 ml of t-butylhydroperoxide, in 60 ml of acetonitrile is refluxed for 48 hours. An additional 1 ml of t-butylhydroperoxide is added after 12 hrs and 24 hrs. Thin layer chromatography after 48 hrs indicates the presence of starting material and the title compound.

EXAMPLE 34 Oxidation of N-methyl 3-(4,6-dimethoxy-2-pyrimidinylmethyl)-5-trimethylsilyl-4-isothiazolecarboxanilide

A mixture of 2.0 g of N-methyl 3-(4,6-dimethoxy-2-pyrimidinylmethyl)-5-trimethylsilyl-4-isothiazolecarboxanilide, 1.5 g of manganese (III) triacetate, 20 ml of acetic acid and 30 ml of methylene dichloride is stirred at RT for 48 hours. The resulting suspension is suction filtered through filter aid and the filter cake washed with water and methylene dichloride. The organic layer is separated, dried and concentrated. The concentrate is flash chromatographed through 300 ml silica gel, 230-400 mesh, using 1 l 70/30 hexane/ethyl acetate, 500 ml 50/50 hexane/ethyl acetate taking 30×50 ml fractions. Fractions 10-15 give a mixture of two components which is heated with boron trifluoride methanol complex (4 drops) in 50 ml of toluene at 80° C. for 2 hrs. The reaction mixture is washed with 30 ml of 15% sodium bicarbonate solution, dried, and concentrated. The concentrate is flash chromatographed through 300 ml silica gel, 230-400 mesh, using 1 l 60/40 hexane/ethyl acetate, 500 ml 40/60 hexane/ethyl acetate and 200 ml ethyl acetate taking 34×50 ml fractions. Fractions 20-23 give N-methyl 3-(4,6-dimethoxy-2-pyrimidinylmethyl)-4-isothiazolecarboxanilide, 0.12 g, mp 92°-93° (Table F, cpd. no. 513). Fractions 24-28 give N-methyl 3-(4,6-dimethoxy-2-pyrimidinylcarbonyl)-4-isothiazolecarboxanilide, 0.3 g, mp 140°-142° C. (Table F, cpd. no. 514).

EXAMPLE 35 3-[(4,6-dimethoxy-2-pyrimidinyl)hydroxy methyl]-N-methyl-2-pyridine carboxamide (Table E, cpd. no. 108)

7.2 g of methylamine gas is bubbled into 300 ml of anhydrous methanol over 10 min at 10°, 30 g of 5-(4,6-dimethoxy-2-pyridimidinyl)furo[3,4-b]-pyridine-7(5H)-one added and the mixture stirred at RT for 14 hours. The reaction mixture is then filtered and the filtrate concentrated to ca 50 ml. The resulting suspension is cooled to ca 10° and the precipitate filtered to isolate the title compound m.p. 132°-133° C.

EXAMPLE 36 3-[(4,6-dimethoxy-2-pyrimidinyl)carbonyl]-2-pyridinecarboxylic acid (Table E, cpd. no. 64)

30.3 g of KMnO₄ and 32.3 g of NaHCO₃ are suspended in 700 ml of water and 57 g of lithium 3-[(4,6-dimethoxy-2-pyrimidinyl)hydroxymethyl]-2-pyridine carboxylate is added with stirring. The reaction mixture is refluxed for 4 hrs and suction filtered hot. The filtrate is cooled over ice water and audified with conc. HCl (60 ml). The precipitated solid is filtered and dried in vacuo at 50° to give the title compound m.p. 159°-161° C.

EXAMPLE 37 5-chloro-5-(4,6-dimethoxy-2-pyrimidinyl)furo[3-b]pyridine-7(5H)-one (Table B, cpd. no. 68)

45.53 g of 3-[(4,6-dimethoxy-2-pyrimidinyl)carbonyl]-2-pyridinecarboxylic acid are suspended in 700 ml of carbon tetrachloride and 186.4 g of thionyl chloride added with stirring. The suspension is heated to 70° C. for 4 hrs and the reaction mixture then cooled to RT and the excess thionyl chloride and carbon tetrachloride evaporated off to give the title compound as a tan solid m.p. 146°-148° C.

EXAMPLE 38 3-[(4,6-dimethoxy-2-pyrimidinyl)carbonyl]-N,N-dimethyl-2-pyridinecarboxamide (Table E, cpd. no. 385)

15.8 g of anhydrous dimethylamine gas is bubbled into 36 g of 5-chloro-5-(4,6-dimethoxy-2-pyrimidinyl)furo[3,4-b]pyridine-7(5H)-one in 350 ml of methylene dichloride cooled in an ice bath and the mixture then stirred overnight at RT. The reaction mixture is then washed with saturated brine solution (3×50 ml) passed through phase separating paper and the filtrate concentrated. The concentrate is dissolved in methylene dichloride, charcoal treated at RT for 1 hr and filtered.

The filtrate is concentrated to 60 ml diluted with hexane, digested for 1 hr at 35° and allowed to crystallize overnight at RT. The precipitate is filtered to isolate 35.15 g of the title product m.p. 124°-126° C.

EXAMPLE 39 3-cyano-4,7-dichloro-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide (Table A, cpd. no. 269)

21.5 g of NaH in oil dispersion are added to 112.75 g of 3-cyano-4,7-dichlorophthalide and 96.7 g of 4,6-dimethoxy-2-methylsulfonyl-pyrimidine. (The hydride is washed with hexane, the hexane removed by suction and the residue covered with DMF and cooled in an ice bath.) The reaction mixture is left to stir overnight at RT and the solution then poured into 3 L of water containing 15 ml of conc. H₂ SO₄ and stirred mechanically until a viscous gum formed around the stirred blade. The water layer is decanted and extracted with 3×400 ml of toluene, the first two extracts added to the gum and the mixture stirred until the gum dissolved. The toluene solution is washed 2×100 ml of water and 1×100 ml of toluene and the combined toluene layers dried over Na₂ SO₄ concentrated to 400 ml and left to stand overnight. The still homogeneous solution is flash-chromatographed over silica gel with toluene (250 ml fraction 5) fractions 5-9 are combined and stripped to give 30 g of the title product m.p. 123°-126° C.

EXAMPLE 40 4,7-dichloro-3-(4,6-dimethoxy-2-pyrimidinyl)-3-hydroxyphthalide (Table A, cpd. no. 250)

70 g of 3-cyano-4,7-dichloro-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide are slurried in 100 ml of methanol and 16 g of NaOH pellets with 125 ml of water added. The mixture is stirred and heated to reflux for 30 mins., the solution cooled and the methanol stripped. The aqueous solution was diluted with 400 ml of water, washed with 100 ml of ether and then added dropwise to 400 ml of 1 NH₂ SO₄ to give a solid which is filtered and dried in vacuum for 1 hr at 60°. The solid is triturated with 100 ml of ether and the suspension left overnight at RT and the solid isolated by filtration to give the title product m.p. 161°-175° C.

EXAMPLE 41 3,6-dichloro-2-[(4,6-dimethoxy-2-pyrimidinyl)carbonyl]benzoic acid, isopropylammonium salt (Table C, cpd. no. 481)

24.13 g of 4,7-dichloro-3-(4,6-dimethoxy-2-pyrimidinyl)-3-hydroxyphthalide is slurried in 500 ml of methylene dichloride and 200 ml of methanol and 125 ml of freshly distilled isopropylamine added. The mixture is heated to reflux and the solution filtered, cooled and stripped. The solid is dried in vacuum for 4 hrs at 45° C. to give the title product m.p. 194°-196° C.

EXAMPLE 42 4,7-dichloro-3-(4,6-dimethoxy-2-pyrimidinyl)-3-hexanoyloxyphthalide (Table A, cpd. no. 265)

52 g of 4,7-dichloro-3-(4,6-dimethoxy-2-pyrimidinyl)-3-hydroxyphthalide and 500 ml of methylene dichloride are cooled in an ice bath and 23 ml of triethylamine and 1.1 g of DMAP added. The mixture is stirred until most of the solid dissolves, 35.2 g of freshly distilled hexanoic anhydride are added and the mixture is stirred for 48 hrs under N₂ at RT. The solution is washed with 2×100 ml 1 NH₂ SO₄, 1×100 ml 0.1N NaOH and brine dried over Na₂ SO₄ and concentrated to give 58.2 g of crude product which is triturated with 150 ml of ether and filtered to isolate the title product m.p. 103°-105° C.

The following compounds may be prepared analogously to the preceding examples or as otherwise described herein. Unless otherwise stated alkyl groups are straight chained i.e. in "n"-form.

    TABLE A       -       ##STR36##       ##STR37##       ##STR38##                melting point       Cpd No Y.sub.1 Y.sub.2 Y.sub.3 Y W.sub.1 W.sub.2 W.sub.3 W.sub.4      R.sub.1 (°C.)       1 H H H OH N CH COCH.sub.3 N OCH.sub.3 136-138       2 H H H H N CH COCH.sub.3 N OCH.sub.3 102-104       3 H H H OCCH.sub.3 N CBr COCH.sub.3 N OCH.sub.3 215-225          O       4 H H H H N CBr CH N OCH.sub.3 136-138       5 H H 5-Cl H N CH COCH.sub.3 N OCH.sub.3 151-153       6 7-Cl H H H N CH COCH.sub.3 N OCH.sub.3 148-149       7 H 6-Cl H H N CH COCH.sub.3 N OCH.sub.3 138-139       8 H H H H N CH CCl N OCH.sub.3 152-153       9 7-Cl H H H N CH CCl N OCH.sub.3 128-130       10 H H 4-Cl H N CH COCH.sub.3 N OCH.sub.3 98-99       11 7-CH.sub.3 H H H N CH COCH.sub.3 N OCH.sub.3 138-140       12 H H H H N CH CCl N CH.sub.3 133-135       13 7-Cl H H OH N CH COCH.sub.3 N OCH.sub.3 188-190        14 7-Cl H H H N CH COiC.sub.3       H.sub.7 N OCH.sub.3 101-102                15 7-OCH.sub.3 H 4-Br H N CH      COCH.sub.3 N OCH.sub.3 126-128        16 7-Cl H H H N CH COCH.sub.2       CF.sub.3 N OCH.sub.3 112-113       17 7-Cl H H H N CH COCH.sub.3 N      ##STR39##       136-138       18 7-Cl H H H N CH      ##STR40##       N OCH.sub.3 115-116       19 7-Cl H H H N CH COCH.sub.3 N      ##STR41##       85-88       20 7-Cl H H H N CH COCH.sub.3 N OC.sub.2       H.sub.5 98-100                   21 7-Cl H H Cl N CH COCH.sub.3 N      OCH.sub.3 163-165        22 7-Cl H H H N CH COCH.sub.2       CCCH.sub.3 N OCH.sub.3 131-133             23 7-Cl H H SCH.sub.3 N CH      COCH.sub.2       CCCH.sub.3 N OCH.sub.3 134-136                                  24 7-Cl      H H H N CH COCH.sub.3 N OCH.sub.2       CHCH.sub.2 72-75                         25 7-Cl H H H N N COCH.sub.3 N O      CH.sub.3 157-160       26 7-OCH.sub.3 H H H N CH COCH.sub.3 N OCH.sub.3 152-154       27 7-Cl H H CN N CH COCH.sub.3 N OCH.sub.3 159-161       28 7-Cl H H CN N N COCH.sub.3 N OCH.sub.3 184-186       29 7-Cl 6-Cl H H N CH COCH.sub.3 N OCH.sub.3 194-195       30 7-Cl H H OCH.sub.3 N CH COCH.sub.3 N OCH.sub.3 180-183       31      ##STR42##       H H CN N CH COCH.sub.3 N OCH.sub.3 169-171       32 7-OCH.sub.3 6-OCH.sub.3 H      ##STR43##       N N COCH.sub.3 N OCH.sub.3 134-136       33 7-Cl H H H N CH CCH.sub.3 N CH.sub.3 164-166       34 H H H      ##STR44##       N CBr CH N OCH.sub.3 163-176       35 H 5-Cl H "H1" N CH COCH.sub.3 N OCH.sub.3 151-153       36 7-Cl H H "H2" N N COCH.sub.3 N OCH.sub.3 126-127       37 H H H OH N CCl COCH.sub.3 N OCH.sub.3 162-165       38 7-F H H CN N CH COCH.sub.3 N OCH.sub.3 132-134       69 7-Cl H H OC.sub.2 H.sub.5 N CH COCH.sub.3 N OCH.sub.3 148-151               72 7-OCH.sub.3 H H CN N CH COCH.sub.3 N OCH.sub.3 159-163       73 H H H CH.sub.3 N CH COCH.sub.3 N OCH.sub.3 87-89                75 H      H H "H1" N CH COCH.sub.3 N OCH.sub.3 168-170       88 7-Cl H H H N CH      ##STR45##       N OCH.sub.3 gum, NMR       98 7-Cl H H H N CH      ##STR46##       N OCH.sub.3 97-98      101 7-Cl H H H N CH       ##STR47##       N H 125-127      102 7-Cl H H H N CH       ##STR48##       N H 83-85      104       ##STR49##       H H CN N CH COCH.sub.3 N OCH.sub.3 105-108      105       ##STR50##       H H OH N CH COCH.sub.3 N OCH.sub.3 109-110      109 7-F H H OCH.sub.3 N CH COCH.sub.3 N OCH.sub.3 172-173.5       113 7-F H H H N CH COCH.sub.3 N OCH.sub.3 138-140       117 7-F H H OH N CH COCH.sub.3 N OCH.sub.3 183.5-185.5       118 7-OH H H CN N CH COCH.sub.3 N OCH.sub.3 121-122      120       ##STR51##       H H CN N CH COCH.sub.3 N OCH.sub.3 174-176      125 7-Cl H H acetoxy N CH COCH.sub.3 N OCH.sub.3 213-215       134 7-OH H H OH N CH COCH.sub.3 N OCH.sub.3 138-141                 (decomp)       135 7CH.sub.3 SO.sub.2 O H H CN N CH COCH.sub.3 N OCH.sub.3 159-161           137 7-OCON(C.sub.2       H.sub.5).sub.2 H H CN N CH COCH.sub.3 N OCH.sub.3 123-125       138 7propargyloxy H H CN N CH COCH.sub.3 N OCH.sub.3 174-175      139       ##STR52##       H H CN N CH COCH.sub.3 N OCH.sub.3 170-171      140       ##STR53##       H H CN N CH COCH.sub.3 N OCH.sub.3 169-172      145       ##STR54##       H H H N CH COCH.sub.3 N OCH.sub.3 108-110      146       ##STR55##       H H H N CH COCH.sub.3 N OCH.sub.3 115-118      147 7-OCH.sub.3 H H OH N CH COCH.sub.3 N OCH.sub.3 174-176       153 7propargyloxy H H H N CH COCH.sub.3 N OCH.sub.3 130-131      154       ##STR56##       H H CN N CH COCH.sub.3 N OCH.sub.3 182-185(decomp)      166 7-OCF.sub.3 H H OH N CH COCH.sub.3 N OCH.sub.3 131-132       167 7-OCH.sub.3 H H acetoxy N CH COCH.sub.3 N OCH.sub.3 201-202                                                                       180       ##STR57##       H H H N CH COCH.sub.3 N OCH.sub.3 133-136      190 7-Oallyl H H H N CH COCH.sub.3 N OCH.sub.3 109-110       195 7-CF.sub.3 O H H acetoxy N CH COCH.sub.3 N OCH.sub.3 165-166                                                                        203      7-Cl H H       ##STR58##       N CH COCH.sub.3 N OCH.sub.3 178-180      204 7-Cl H H       ##STR59##       N CH COCH.sub.3 N OCH.sub.3 131-133      205 7-Cl H H       ##STR60##       N CH COCH.sub.3 N OCH.sub.3 177-179      208 7-Cl H H benzoyloxy N CH COCH.sub.3 N OCH.sub.3 192-194      240 7-Cl H H       ##STR61##       N CH COCH.sub.3 N OCH.sub.3 158-160      250 7-Cl H 4-Cl OH N CH COCH.sub.3 N OCH.sub.3 171-175       253 7-Cl H H cinnamoyloxy N CH COCH.sub.3 N OCH.sub.3 221-224      256 7-Cl H H       ##STR62##       N CH COCH.sub.3 N OCH.sub.3 102-103      258 7-Cl H H 2-butenoxy N CH COCH.sub.3 N OCH.sub.3 102-103      263 7-Cl H 4-Cl       ##STR63##       N CH COCH.sub.3 N OCH.sub.3 163-164      265 7-Cl H 4-Cl       ##STR64##       N CH COCH.sub.3 N OCH.sub.3 87-91      266 7-Cl H 4-Cl       ##STR65##       N CH COCH.sub.3 N OCH.sub.3 137-138      267 7-Cl H 4-Cl       ##STR66##       N CH COCH.sub.3 N OCH.sub.3 128-131      268 7-F H 4-F CN N CH COCH.sub.3 N OCH.sub.3 135-136       269 7-Cl H 4-Cl CN N CH COCH.sub.3 N OCH.sub.3 123-126       270 7-Cl H 4-Cl H N CH COCH.sub.3 N OCH.sub.3 156-161       307 4-Cl H H OH N CH COCH.sub.3 N OCH.sub.3 146-150       319 4-Cl H H CN N CH COCH.sub.3 N OCH.sub.3 132-133       320 4-Cl H H OCH.sub.3 N CH COCH.sub.3 N OCH.sub.3 168-168.5      326 7-Cl H H       ##STR67##       N CH COCH.sub.3 N OCH.sub.3 142-143      409 7-Cl H H       ##STR68##       N CH COCH.sub.3 N OCH.sub.3 162-163      452 7-Cl 4-Cl H OCH.sub.2 CHCH.sub.2 N CH COCH.sub.3 N OCH.sub.3 135-136       459 7-OCH.sub.3 4-Cl H OH N CH COCH.sub.3 N OCH.sub.3 212-213       476 7-Si(CH.sub.3).sub.3 H H OH N CH COCH.sub.3 N OCH.sub.3 103-104           477 7-OCH.sub.3 4-Cl H H N CH COCH.sub.3 N OCH.sub.3 183-185              486 7-Cl 4-Cl H Cl N CH COCH.sub.3 N OCH.sub.3 139-142       526 7-Cl 4-F H OH N CH COCH.sub.3 N OCH.sub.3 178-179      543 7-Cl 4-CH.sub.3 H       ##STR69##       N CH COCH.sub.3 N OCH.sub.3 95-96      549 7-Cl 4-0CH.sub.3 H       ##STR70##       N CH COCH.sub.3 N OCH.sub.3 116-117      568 7-Cl 4-Cl H CN N CCl COCH.sub.3 N OCH.sub.3 188.5-189      580 7-CH.sub.3 4-F H       ##STR71##       N CH COCH.sub.3 N OCH.sub.3 103-104.5      582 7-CH.sub.3 4-F H H N CH COCH.sub.3 N OCH.sub.3 138-140      588 7-SO.sub.2       CH.sub.3 H H      ##STR72##       N CH COCH.sub.3 N OCH.sub.3 146-148      590 7-Cl 4-Cl H       ##STR73##       N CH COCH.sub.3 N OCH.sub.3 145-148      591 7-Cl 4-Cl H       ##STR74##       N CH COCH.sub.3 N OCH.sub.3 130-132      595 7-Cl 4-Cl H       ##STR75##       N CH COCH.sub.3 N OCH.sub.3 127-129      597 7-Cl 4-NO.sub.2 H CN N CH COCH.sub.3 N OCH.sub.3 151.5-152.5                                                                       599      7-Cl 4-Cl H       ##STR76##       N CH COCH.sub.3 N OCH.sub.3 171-174      605 7-Cl 4-Cl H       ##STR77##       N CH COCH.sub.3 N OCH.sub.3 81-83      606 7-Cl 4-Cl H       ##STR78##       N CH COCH.sub.3 N OCH.sub.3 103-108      607 7-Cl 4-Cl H       ##STR79##       N CH COCH.sub.3 N OCH.sub.3 98-101      608 7-Cl 4-Cl H       ##STR80##       N CH COCH.sub.3 N OCH.sub.3 83-85      610 7-CH.sub.3 4-Cl H       ##STR81##       N CH COCH.sub.3 N OCH.sub.3 114-115      611 7-Cl 5-Cl H       ##STR82##       N CH COCH.sub.3 N OCH.sub.3 206-210      612 7-Cl 4-F H       ##STR83##       N CH COCH.sub.3 N OCH.sub.3 122-123      615 7-Br H H       ##STR84##       N CH COCH.sub.3 N OCH.sub.3 142-144       618 7-CN H H       ##STR85##       N CH COCH.sub.3 N OCH.sub.3 160-162       623 7-Cl 4-Cl H OCH.sub.3 N CH COCH.sub.3 N OCH.sub.3 184-185       624 7-Cl 4-CH.sub.3 H OCH.sub.3 N CH COCH.sub.3 N OCH.sub.3 178-179

                                      TABLE B                                      __________________________________________________________________________                  ##STR86##                                                                                  ##STR87##                                                                                                        melting             Cpd                                                        point               No W.sub.7                                                                              W.sub.8                                                                             W.sub.9                                                                             W.sub.10                                                                             Y        W.sub.1                                                                           W.sub.2                                                                           W.sub.3    W.sub.4                                                                           R.sub.1                                                                             (°C.)        __________________________________________________________________________      39                                                                               CH    CH   CH   N     H        N  CH COCH.sub.3 N  OCH.sub.3                                                                           149-                                                                           151                  40                                                                               N     CH   CH   CH    H        N  CH COCH.sub.3 N  OCH.sub.3                                                                           167-                                                                           168                  41                                                                               CH    CH   N    CH    H        N  CH COCH.sub.3 N  OCH.sub.3                                                                           oil                                                                            NMR                  42                                                                               CH    N    CH   CH    H        N  CH COCH.sub.3 N  OCH.sub.3                                                                           120-                                                                           126                  43                                                                               N     CCl  CH   CH    H        N  CH COCH.sub.3 N  OCH.sub.3                                                                           166-                                                                           169                  44                                                                               N     CH   CC.sub.2 H.sub.5                                                                    CH    H        N  N  COCH.sub.3 N  OCH.sub.3                                                                           oil                                                                            NMR                  45                                                                               N     CH   CH   CH    H        N  N  COCH.sub.3 N  OCH.sub.3                                                                           75-80                46                                                                               CH    CC.sub.2 H.sub.5                                                                    CH   N     H        N  CH COCH.sub.3 N  OCH.sub.3                                                                           oil                                                                            NMR                  47                                                                               CH    CH   CH   N     CH.sub.3 N  CH COCH.sub.3 N  OCH.sub.3                                                                           98-101               68                                                                               N     CH   CH   CH    Cl       N  CH COCH.sub.3 N  OCH.sub.3                                                                           146-                                                                           148                  70                                                                               N     CH   CH   CH    "H1"     N  CH COCH.sub.3 N  OCH.sub.3                                                                           173-                                                                           176                  89                                                                               CCH.sub.3                                                                            CH   CH   N     H        N  CH COCH.sub.3 N  OCH.sub.3                                                                           129-                                                                           131                  92                                                                               N     CH   CH   CH    H        N  CH COCH.sub.2 CF.sub.3                                                                       N  OCH.sub.3                                                                           116-                                                                           119                  93                                                                               N     CH   CH   CH    H        N  CH CCH.sub.3  N  CH.sub.3                                                                            193-                                                                           195                  94                                                                               N     CH   CH   CH    H        N  CH CCl        N  OCH.sub.3                                                                           147-                                                                           149                  95                                                                               N     CH   CH   CH    H        N  CH                                                                                 ##STR88## N  OCH.sub.3                                                                           oil NMR              99                                                                               N     CH   CH   CH    H        N  CH COC.sub.3 H.sub.7                                                                         N  OCH.sub.3                                                                           140-                                                                           142                 100                                                                               N     CH   CH   CH    H        N  CH COC.sub.2 H.sub.5                                                                         N  OCH.sub.3                                                                           133-                                                                           135                 106                                                                               N     CH   CH   CH    H        N  CH COallyl    N  OCH.sub.3                                                                           112-                                                                           114                 107                                                                               N     CH   CH   CH    H        N  CH COCH.sub.2 CCCH.sub.3                                                                     N  OCH.sub.3                                                                           oil                                                                            NMR                 114                                                                               CCl   N    CH   CH    H        N  CH COCH.sub.3 N  OCH.sub.3                                                                           168-                                                                           170                 121                                                                               COCH.sub.3                                                                           N    CH   CH    H        N  CH COCH.sub.3 N  OCH.sub.3                                                                           150-                                                                           153                                                                            (de-                                                                           comp)               136                                                                               N     CH   CH   CH    H        N  CH COCH.sub.3 N  H    158-                                                                           160                 141                                                                               N     CH   CH   CH    *        N  CH COCHF.sub.2                                                                               N  OCHF.sub.2                                                                          145-                                                                           147                 148                                                                               CH    CH   CH   N     "H1"     N  CH COCH.sub.3 N  OCH.sub.3                                                                           212-                                                                           213                 175                                                                               CH    CH   CH   N     OH       N  CH COCH.sub.3 N  OCH.sub.3                                                                           172-                                                                           178                 260                                                                               CCH.sub.3                                                                            N    CH   CH    OH       N  CH COCH.sub.3 N  OCH.sub.3                                                                           203-                                                                           204                 261                                                                               CCOOH N    CH   CH    OH       N  CH COCH.sub.3 N  OCH.sub.3                                                                           130-                                                                           132                                                                            (de-                                                                           comp)               317                                                                               N     CH   CH   CH    H        N  CH COCH.sub.3 N  CH.sub.3                                                                            138-                                                                           140                 408                                                                               N     CH   CH   CH    N(CH.sub.3)OCH.sub.3                                                                    N  CH COCH.sub.3 N  OCH.sub.3                                                                           168-                                                                           170                 572                                                                               N     CH   CH   COCH.sub.3                                                                           CN       N  CH COCH.sub.3 N  OCH.sub.3                                                                           177-                                                                           179                 629                                                                               N     CH   CH   CH    (1)      N  CH COCH.sub.3 N  OCH.sub.3                                                                           148-                                                                           150                 630                                                                               N     CH   CH   CH    (2)      N  CH COCH.sub.3 N  OCH.sub.3                                                                           155-                                                                           159                 631                                                                               N     CH   CH   CH    (3)      N  CH COCH.sub.3 N  OCH.sub.3                                                                           199-                                                                           200                 636                                                                               N     CH   CH   CH    (4)      N  CH COCH.sub.3 N  OCH.sub.3                                                                           200-                                                                           204                 637                                                                               N     CH   CH   CH    (5)      N  CH COCH.sub.3 N  OCH.sub.3                                                                           215-                                                                           217                 __________________________________________________________________________      (1) =                                                                          ##STR89##                                                                      (2) =                                                                          ##STR90##                                                                      (3) =                                                                          ##STR91##                                                                      (4) =                                                                          ##STR92##                                                                      (5) =                                                                          ##STR93##                                                                

    TABLE C       -       ##STR94##                  melting point       Cpd # Y.sub.1 Y.sub.2 Y.sub.3 R X Y W.sub.1 W.sub.2 W.sub.3 W.sub.4      R.sub.1 (°C.)       48 H H H      ##STR95##       H H N CH COCH.sub.3 N OCH.sub.3 oil NMR       49 H H H " O N CH COCH.sub.3 N OCH.sub.3 oil NMR       50 H H H      ##STR96##       H H N CH COCH.sub.3 N OCH.sub.3 150-152       51 H H H COOH NH N CH COCH.sub.3 N OCH.sub.3 225-235                 (free acid)       52 2-Cl H H CN H H N CH COCH.sub.3 N OCH.sub.3 94-95       53 2-Cl H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 153-157                   (Li.sup.+       salt)       54 2-Cl H H      ##STR97##        OCH.sub.3 N CH COCH.sub.3 N OCH.sub.3 oil NMR       55 2-Cl H H COOCH.sub.3 O N CH COCH.sub.3 N OCH.sub.3 110-111        56 2-Cl H H CONHCH.sub.3 OH H N CH COCH.sub.3 N OCH.sub.3 130-132             57 2-Cl H H CON(CH.sub.3).sub.2 O N CH COCH.sub.3 N OCH.sub.3      141-142       58 2-Cl H H COOH O N CH COCH.sub.3 N OCH.sub.3 276-278                 (Na.sup.+       salt)       59 2-Cl H H      ##STR98##       OCH.sub.3 H N CH COCH.sub.3 N OCH.sub.3 148-150       60 H H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 185 (dec.)                   (Li.sup.+       salt)       61 H H H      ##STR99##       H H N CH CCl N Cl NMR       62 H H H " Br H N CH COCH.sub.3 N OCH.sub.3       71 H H H COOH OH H1 N CH COCH.sub.3 N OCH.sub.3       74 H H H COOH OH CH.sub.3 N CH COCH.sub.3 N OCH.sub.3 >250                   (Li.sup.+       salt)                                               76 2-Cl H H      COOC.sub.2       H.sub.5 O N CH COCH.sub.3 N OCH.sub.3 66-67                     77 2Cl      H H COOallyl O N CH COCH.sub.3 N OCH.sub.3 81-83       78 2Cl H H COObuten-3-yl O N CH COCH.sub.3 N OCH.sub.3 48-50       79 2Cl H H COObenzyl O N CH COCH.sub.3 N OCH.sub.3 99-101       80 2Cl H H      ##STR100##        OH N CH COCH.sub.3 N OCH.sub.3 99-101       81 2Cl H H      ##STR101##        OH N CH COCH.sub.3 N OCH.sub.3 153-154       85 2Cl H H CON(C.sub.2 H.sub.5).sub.2 O N CH COCH.sub.3 N OCH.sub.3      110-111       86 H H H COObenzyl OH H N CH COCH.sub.3 N OCH.sub.3 oil NMR       87 2Cl H H      ##STR102##        OH N CH COCH.sub.3 N OCH.sub.3 161-163       96 2-Cl H H CON(C.sub.2 H.sub.5).sub.2 OH H N CH COCH.sub.3 N OCH.sub.3      74-80       103 2-Cl H H CONCH.sub.3 (benzyl) O N CH COCH.sub.3 N OCH.sub.3 105-107       115 2-F H H COOCH.sub.3 O N CH COCH.sub.3 N OCH.sub.3 101-104       116 2-F H H COOallyl O N CH COCH.sub.3 N OCH.sub.3 97-99       122 H H H COOallyl O N CH COCH.sub.3 N OCH.sub.3 92-93       123 2-Cl H H COO 2-methyl- O N CH COCH.sub.3 N OCH.sub.3 137-139                  allyl       124 2-Cl H H COO-3-methyl- O N CH COCH.sub.3 N OCH.sub.3 54-57           but-2-enyl       126 2-Cl H H COOpropargyl O N CH COCH.sub.3 N OCH.sub.3 138-140               143 2-Cl H H COObut-2-enyl O N CH COCH.sub.3 N OCH.sub.3 61-65        156 2-OCH.sub.3 H H COOCH.sub.3 O N CH COCH.sub.3 N OCH.sub.3 142-143        163 2-F H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+ salt                          220-240 (decomp)       165 2OCH.sub.3 H H COOallyl O N CH COCH.sub.3 N OCH.sub.3 100-101       181       ##STR103##       H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+       salt158-159                                                         191 2OCF.sub.3 H H      COOCH.sub.3 O N CH COCH.sub.3 N OCH.sub.3 80-82 (decomp)       192 3-Cl H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+ salt                          170-174 (decomp)       194 5-Cl H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+ salt                          225-227 (decomp)       197 4-Cl H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+ salt                          195-198 (decomp)       202 2-pro- H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+ salt             pargyloxy           >200 (decomp)       218 2-Cl H H       ##STR104##       O N CH COCH.sub.3 N OCH.sub.3 oil NMR      219 2-Cl H H       ##STR105##       O N CH COCH.sub.3 N OCH.sub.3 127-128      220 2-Cl H H       ##STR106##       O N CH COCH.sub.3 N OCH.sub.3 154-155       222 2-OC.sub.3 H.sub.7 H H COOH OH H N CH COCH.sub.3 N OCH.sub.3      Li.sup.+       salt           >273 (decomp)       228 2-Cl 5-Cl H COOH O N CH COCH.sub.3 N OCH.sub.3 Na.sup.+ salt                         >210 (decomp)       235 2-Cl 5-Cl H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Na.sup.+ salt                       >205 (decomp)       239 2-Cl H H COOCH.sub.2 CHCHCl O N CH COCH.sub.3 N OCH.sub.3 86-87       242 2-Cl H H       ##STR107##       OCH.sub.3 H N CH COCH.sub.3 N OCH.sub.3 112-113                                                                               2      43 H H H COOH O N CH COCH.sub.3 N OCH.sub.3 Na.sup.+       salt                            >295 (decomp)       244 2-F H H COOH O N CH COCH.sub.3 N OCH.sub.3 Li.sup.+       salt                        276 (decomp)       247 2-Cl H H COOC.sub.3 H.sub.7 O N CH COCH.sub.3 N OCH.sub.3 63-65           249 2-Cl 5-Cl H COOCH.sub.3 O N CH COCH.sub.3 N OCH.sub.3 130-132         251 2-Cl H H COOCH.sub.2 CHCHCl O N CH COCH.sub.3 N OCH.sub.3 107-108       262 2-Cl 5-Cl H COOallyl O N CH COCH.sub.3 N OCH.sub.3 89-90       264 2-Cl 5-Cl H COOC.sub.12 H.sub.25 O N CH COCH.sub.3 N OCH.sub.3 oil      NMR       274 2-F 5-F H COOH O N CH COCH.sub.3 N OCH.sub.3 Na.sup.+       salt                      >295 (decomp)       277 2-Cl H H COOC.sub.4 H.sub.9 O N CH COCH.sub.3 N OCH.sub.3 NMR             281 2-Cl H H COOC.sub.5 H.sub.11 O N CH COCH.sub.3 N OCH.sub.3      NMR       287 2-Cl H H COOC.sub.6 H.sub.13 O N CH COCH.sub.3 N OCH.sub.3 70-71          299 2-Cl H H COOC.sub.7 H.sub.15 O N CH COCH.sub.3 N OCH.sub.3 NMR         300 2-Cl H H COOC.sub.8 H.sub.17 O N CH COCH.sub.3 N OCH.sub.3 NMR          306 5-Cl H H COOH O N CH COCH.sub.3 N OCH.sub.3 Na.sup.+ salt                         266-276 (decomp)       308 2-Cl H H COOC.sub.12 H.sub.25 O N CH COCH.sub.3 N OCH.sub.3 NMR                                                                           314      2-Cl H H       ##STR108##       O N CH COCH.sub.3 N OCH.sub.3 92-94                                                                               3      15 2-Cl H H CH.sub.2 OH OH H N CH COCH.sub.3 N OCH.sub.3 115-116               316 2-Cl H H COOiC.sub.3 H.sub.7 O N CH COCH.sub.3 N OCH.sub.3      109-110       321 5-Cl H H COOCH.sub.3 O N CH COCH.sub.3 N OCH.sub.3 115-116       423 5-Cl H H COOallyl O N CH COCH.sub.3 N OCH.sub.3 117-118       425 2-Cl H H CH.sub.2       O  OH N CH COCH.sub.3 N OCH.sub.3 92-94            460 2-OCH.sub.3 5-Cl H       COOH O N CH COCH.sub.3 N OCH.sub.3 Na.sup.+       salt                                    228-230       461 2-OCH.sub.3 5-Cl H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3      N.sup.+ iC.sub.3       H.sub.7 salt      190-201       478 2-OCH.sub.3 5-Cl H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+      salt                   150-160       479 2-Cl 5-Cl H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.2 N.sup.+      (iC.sub.3       H.sub.7).sub.2 salt         160-162       480 2-Cl 5-Cl H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.2 N.sup.+      (CH.sub.3).sub.2 salt                  152-154       481 2-Cl 5-Cl H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3 N.sup.+      iC.sub.3       H.sub.7 salt          184-186       489 2-Cl 5-Cl H CON(CH.sub.3).sub.2 O N CH COCH.sub.3 N OCH.sub.3      145-147       502 2-Cl H H COOH O N CH COCH.sub.3 N OCH.sub.3 NH.sub.4 salt                  157-160       503 2-Cl H H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3 N.sup.+      iC.sub.3       H.sub.7 salt          136-139       504 2-Cl H H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.2 N.sup.+      (CH.sub.3).sub.2 salt                  163-165       527 2-Cl 5-F H CON(CH.sub.3).sub.2 O N CH COCH.sub.3 N OCH.sub.3      113-114       528 2-Cl 5-F H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3 N.sup.+      iC.sub.3       H.sub.7 salt          174-176 (decomp)       531 2-Cl 5-Cl H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3 N.sup.+      C.sub.2 H.sub.4 OC.sub.2 H.sub.4       OH.sup.(1) salt                                     81-83       532 2-Cl H H COOH O N CH COCH.sub.3 N OCH.sub.3 DGA salt                  gum       533 2-Cl 5-CH.sub.3 H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3      N.sup.+ iC.sub.3       H.sub.7 salt      156-159       534 2-Cl 5-OCH.sub.3 H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3      N.sup.+ iC.sub.3       H.sub.7 salt      182-184       535 2-CH.sub.3 5-F H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3 N.sup.+      iC.sub.3       H.sub.7 salt          161-162       536 2-CH.sub.3 5-Cl H COOH O N CH COCH N OCH.sub.3 H.sub.3 N.sup.+      iC.sub.3       H.sub.7 salt          164-165       537 2-Cl 4-Cl H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3 N.sup.+      iC.sub.3       H.sub.7 salt          150-151       538 2-SCH.sub.3 H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Na.sup.+ salt                   205-215 (decomp)       539 2-Cl 5-F H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Na.sup.+ salt                        216-225 (decomp)       542 2-Cl 5-CH.sub.3 H CON(CH.sub.3).sub.2 O N CH COCH.sub.3 N OCH.sub.3 1      28-129       544 2-Cl 5-CH.sub.3 H COOCH.sub.3 O N CH COCH.sub.3 N OCH.sub.3 87-88      545 2-Cl 5-Cl H       ##STR109##       O N CH COCH.sub.3 N OCH.sub.3 102-104      547 2-Cl 5-Cl H       ##STR110##       O N CH COCH.sub.3 N OCH.sub.3 95-97      548 2-Cl 5-OCH.sub.3 H CON (CH.sub.3).sub.2 O N CH COCH.sub.3 N OCH.sub.3       130-131       550 2-Cl 5-OCH.sub.3 H COOH O N CH COCH N OCH.sub.3 Na.sup.+ salt                        225-227 (decomp)       556 2-Cl 5-OCH.sub.3 H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+      salt                   182-185 (decomp)       557 2-Cl 5-OCH.sub.3 H COOCH.sub.3 O N CH COCH.sub.3 N OCH.sub.3      144-145       559 2-CF.sub.3 H H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3 N.sup.+      iC.sub.3       H.sub.7 salt          124-125       560 2-CF.sub.3 H H CON(CH.sub.3).sub.2 O N CH COCH.sub.3 N OCH.sub.3      94-95       561 2-CF.sub.3 H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+ salt                    95-100 (decomp)       563 2-SO.sub.2 CH.sub.3 H H COOH OH H N CH COCH.sub.3 N OCH.sub.3      Na.sup.+       salt           191-198 (decomp)       566 2-CH.sub.3 H H COOH O N CH COCH.sub.3 N OCH.sub.3 Li.sup.+ salt                      >260       567 2-CH.sub.3 H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+ salt                    190-199       570 2-SCH.sub.3 5-Cl H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+      salt                   183-185       577 2-Cl 5-Cl H       ##STR111##       O N CH COCH.sub.3 N OCH.sub.3 53-56      578 2-Cl 5-Cl H       ##STR112##       O N CH COCH.sub.3 N OCH.sub.3 134-136       581 2-CH.sub.3 5-F H CON(CH.sub.3).sub.2 O N CH COCH.sub.3 N OCH.sub.3      125-127       583 2-SCH.sub.3 H H COOH O N CH COCH.sub.3 N OCH.sub.3 Na.sup.+ salt                     286-289 (decomp)       585 2-NH.sub.2 H H COOH O N CH COCH.sub.3 N OCH.sub.3 Na.sup.+ salt                      265-270 (decomp)       586 2-SO.sub.2 CH.sub.3 H H COOH O N CH COCH.sub.3 N OCH.sub.3 Na.sup.+      salt                  265-266       587 2-SO.sub.2 CH.sub.3 H H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3      N.sup.+ iC.sub.3       H.sub.7 salt      84-90 (decomp)       589 2-CH.sub.3 5-F H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+      salt                   176-181 (decomp)       592 2-SO.sub.2 CH.sub.3 5-Cl H COOH OH H N CH COCH.sub.3 N OCH.sub.3      Li.sup.+       salt           213-216 (decomp)       593 2-Cl 5-Cl H       ##STR113##       O N CH COCH.sub.3 N OCH.sub.3 165-166      594 2-Cl 5-Cl H       ##STR114##       O N CH COCH.sub.3 N OCH.sub.3 123-125                                                                               5      96 2-Cl 5-NO.sub.2 H CN CN H N CH COCH.sub.3 N OCH.sub.3 174.5-175.5           600 2-Cl 5-NO.sub.2 H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3      N.sup.+ iC.sub.3       H.sub.7 salt      168-170      604 2-Cl 5-Cl H       ##STR115##       O N CH COCH.sub.3 N OCH.sub.3 143-144       613 2-Br H H CON(CH.sub.3).sub.2 O N CH COCH.sub.3 N OCH.sub.3 134-135        614 2-Br H H COOH O N CH COCH.sub.3 N OCH.sub.3 Na.sup.+       salt                      285-286       616 2-Br H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Na.sup.+ salt                          166-174 (decomp)       617 2-CN H H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3 N.sup.+      iC.sub.3       H.sub.7 salt          160-162       619 2-CN H H COOH O N CH COCH.sub.3 N OCH.sub.3 Na.sup.+       salt                       293-295 (decomp)       620 2-CN H H CON(CH.sub.3).sub.2 O N CH COCH.sub.3 N OCH.sub.3 150-151        621 2-CN H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 Na.sub.+ salt                         118-125 (decomp)       627 2-Cl 5-Cl H CN CN H N CH COCH.sub.3 N OCH.sub.3 134-136       628 2-Cl 3-Cl H CN CN H N CH COCH.sub.3 N OCH.sub.3 122-125      .sup.(1) H.sub.3 N.sup.+ C.sub.2 H.sub.4 OC.sub.2 H.sub.4 OH is also know      as diglycolamine or DGA

                                      TABLE D                                      __________________________________________________________________________      ##STR116##                                                                                                                             melting                                                                        point                 Cpd No                                                                              A (anti clockwise)*                                                                        R            X    Y  W.sub.1                                                                           W.sub.2                                                                           W.sub.3                                                                              W.sub.4                                                                           R.sub.1                                                                            (°C.)          __________________________________________________________________________      65  SCHCH                                                                                       ##STR117##       H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          125-127                66  SCHCH                                                                                       ##STR118##       H  N  N  COCH.sub.3                                                                           N  OCH.sub.3                                                                          oil NMR                67  CHCHCHN     COOH         OH   CH.sub.3                                                                          N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          Li.sup.+ salt                                                                  >283                                                                           (decomp)              119                                                                                  ##STR119## CONHCH.sub.3 OH   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          oil NMR               142  CHCHCHN     COOC.sub.2 H.sub.5                                                                          CN   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          109-111               149  CHCHCHN     COOH         OH   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          Li.sup.+ salt                                                                  160-165                                                                        (decomp)              150  CHCHCHN     CONHC.sub.3 H.sub.7                                                                         OH   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          oil NMR               173  CHCHCHN     COOH         OH   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          142-145                                                                        (decomp)              174  CHCHCHN     COOCH.sub.3  OH   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          oil NMR               176  CHCHCHN     COOCH.sub.3  O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          129-131               178                                                                                  ##STR120## COOCH.sub.3  H    H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          oil NMR               179                                                                                  ##STR121## COOH         H    H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          Li.sup.+ salt                                                                  >240 (decomp)         186                                                                                  ##STR122## COOCH.sub.3  O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          147-149               187                                                                                  ##STR123## COOH         O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          Na.sup.+ salt                                                                  235                   198                                                                                  ##STR124## COOCH.sub.3  Br   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          125-126               199  CHCHCHN     COOH         OH   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          Na.sup.+ salt                                                                  242 (decomp)          206                                                                                  ##STR125## COOCH.sub.3  acetoxy                                                                             H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          oil NMR               216                                                                                  ##STR126## COOC.sub.2 H.sub.5                                                                          H    H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          oil NMR               236                                                                                  ##STR127## COOC.sub.2 H.sub.5                                                                          Br   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          oil NMR               237                                                                                  ##STR128## COOC.sub.2 H.sub.5                                                                          Br   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          oil NMR               238                                                                                  ##STR129## COOC.sub.2 H.sub.5                                                                          Br   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          oil NMR               248                                                                                  ##STR130## COOC.sub.2 H.sub.5                                                                          O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          103-104               254                                                                                  ##STR131## COOH         O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          180-185 (decomp)                                                               .                     301  CHCHCHN     CON(C.sub.2 H.sub.5).sub.2                                                                  H    H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          69-72                 302  CHCHCHN     COOH         OH   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          K.sup.+ salt                                                                   220-230                                                                        (decomp)              330  CHCHCHN     CON(C.sub.2 H.sub.5).sub.2                                                                  OtC.sub.4 H.sub.9                                                                   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          oil NMR               414  NCHCHCH                                                                                     ##STR132##       OH N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          136-138               415  CHCHCHN                                                                                     ##STR133##  O       CH CH CH    CH CF.sub.3                  416  CHCHCHN                                                                                     ##STR134##  OH   H  CH CH CH    CH CF.sub.3                  417  CHCHCHN                                                                                     ##STR135##  OH   H  CH CH CH    CH CF.sub.3                  418  CHCHCHN                                                                                     ##STR136##  OH   H  CH CH CH    CH CF.sub.3                  419  NCHCHCH                                                                                     ##STR137##  O       CH CH CH    CH CF.sub.3                  420  NCHCHCH                                                                                     ##STR138##  OH   H  CH CH CH    CH CF.sub.3                  421  NCHCHCH                                                                                     ##STR139##  OH   H  CH CH CH    CH CF.sub.3                  422  NCHCHCH                                                                                     ##STR140##  OH   H  CH CH CH    CH CF.sub.3                  426  NCHCHCH                                                                                     ##STR141##       OH N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          163-165               511                                                                                  ##STR142## COOCH.sub.3  O(t)C.sub.4 H.sub.9                                                                 H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          115-117               512                                                                                  ##STR143## CONHC.sub.6 H.sub.13                                                                        OH   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          94-97                 518                                                                                  ##STR144## COOH         O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          NMR                   523                                                                                  ##STR145## COOC.sub.2 H.sub.5                                                                          H    H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          NMR                   524                                                                                  ##STR146## COOC.sub.2 H.sub.5                                                                          O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          98-99                 525                                                                                  ##STR147## COOH         O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          Li.sup.+ salt                                                                  >280°          529                                                                                  ##STR148## COOC.sub.2 H.sub.5                                                                          H    H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          83-85                 540                                                                                  ##STR149## COOC.sub.2 H.sub.5                                                                          O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          163-165               541                                                                                  ##STR150## COOH         O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          Li.sup.+ salt                                                                  275-280               551                                                                                  ##STR151## CON(CH.sub.3).sub.2                                                                         O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          138-140               552                                                                                  ##STR152## COOC.sub.2 H.sub.5                                                                          H    H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          89-92                 553                                                                                  ##STR153## COOC.sub.2 H.sub.5                                                                          Br   H  N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          NMR                   554                                                                                  ##STR154## COOC.sub.2 H.sub.5                                                                          O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          116-118               555                                                                                  ##STR155## COOH         O       N  CH COCH.sub.3                                                                           N  OCH.sub.3                                                                          Li.sup.+ salt                                                                  >275                  __________________________________________________________________________      *Left hand atom attached to Rbearing carbon                              

    TABLE E       -       ##STR156##                                                                               C      pd # Y.sub.1 Y.sub.2 Y.sub.3 R X Y W.sub.1 W.sub.2 W.sub.3 W.sub.4      R.sub.1 m.p.       63 H H H COOH O N CH COCH.sub.3 N OCH.sub.3 164-166       64 H H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 90-92       82 H H H CONH.sub.2 OH H N CH COCH.sub.3 N OCH.sub.3 135-137       83 H H H CONHbenzyl OH H N CH COCH.sub.3 N OCH.sub.3 NMR       84 H H H CONHallyl OH H N CH COCH.sub.3 N OCH.sub.3 NMR       91 H H H COOCH.sub.3 O N CH COCH.sub.3 N OCH.sub.3 119-121       97 H H H COObenzyl OH H N CH COCH.sub.3 N OCH.sub.3 NMR      108 H H H CONHCH.sub.3 OH H N CH COCH.sub.3 N OCH.sub.3 127-129       110 H H H CONHC.sub.3 H.sub.7 OH H N CH COCH.sub.3 N OCH.sub.3 oil NMR        111 H H H CONHC.sub.6 H.sub.13 OH H N CH COCH.sub.3 N OCH.sub.3 67-69        112 H H H CONH(i)C.sub.3 H.sub.7 OH H N CH COCH.sub.3 N OCH.sub.3 oil      NMR       127 H H H CONHallyl benzoyloxy H N CH COCH.sub.3 N OCH.sub.3 NMR              128 H H H CONHallyl acetoxy H N CH COCH.sub.3 N OCH.sub.3 NMR          129 H H H CONH.sub.2 ethoxy- H N CH COCH.sub.3 N OCH.sub.3 112-114              carbonyloxy       130 H H H CONHC.sub.12 H.sub.25 OH H N CH COCH.sub.3 N OCH.sub.3 oil      NMR       131 H H H CONHC.sub.2 H.sub.4       OCH.sub.3 OH H N CH COCH.sub.3 N OCH.sub.3 79-80       132 H H H CONH.sub.2 NH.sub.2 OH H N CH COCH.sub.3 N OCH.sub.3 75-78          133 H H H CONHallyl OCONHCH.sub.3 H N CH COCH.sub.3 N OCH.sub.3 NMR        144 H H H CONHpropargyl OH H N CH COCH.sub.3 N OCH.sub.3 102-104                                                                         151 H      H H       ##STR157##       OH H N CH COCH.sub.3 N OCH.sub.3 oil NMR      152 H H H       ##STR158##       OH H N CH COCH.sub.3 N OCH.sub.3 oil NMR      155 H H H CONHC.sub.18 H.sub.37 OH H N CH COCH.sub.3 N OCH.sub.3 64-66      157 H H H       ##STR159##       OH H N CH COCH.sub.3 N OCH.sub.3 102-104      158 H H H CONH.sub.2 benzoyloxy H N CH COCH.sub.3 N OCH.sub.3 115-116          159 H H H CON(benzoyl).sub.2 benzoyloxy H N CH COCH.sub.3 N OCH.sub.3       168-170      160 H H H       ##STR160##       OH H N CH COCH N OCH.sub.3 88-90      161 H H H CONH.sub.2       ##STR161##       H N CH COCH.sub.3 N OCH.sub.3 138-140      162 H H H       ##STR162##       ##STR163##       H N CH COCH.sub.3 N OCH.sub.3 198-200      164 H H H       ##STR164##       OH N H CH COCH.sub.3 N OCH.sub.3 91-94      168 H H H       ##STR165##       OH H N CH COCH.sub.3 N OCH.sub.3 103-106      169 H H H       ##STR166##        H N CH COCH.sub.3 N OCH.sub.3 135-137      170 H H H CONHNH(t)C.sub.4 H.sub.9 OH H N CH COCH.sub.3 N OCH.sub.3      109-110      171 H H H       ##STR167##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      172 H H H       ##STR168##       OH H N CH COCH.sub.3 N OCH.sub.3 140-142      177 H H H CONHC.sub.2 H.sub.4 N(CH.sub.3).sub.2 OH H N CH COCH.sub.3 N      OCH.sub.3 NMR      182 H H H       ##STR169##       OH H N CH COCH.sub.3 N OCH.sub.3 117-120      183 H H H       ##STR170##       OH H N CH COCH.sub.3 N OCH.sub.3 132-133      184 H H H       ##STR171##       OH H N CH COCH.sub.3 N OCH.sub.3 113-114      185 H H H CONHSO.sub.2 CH.sub.3 OH H N CH COCH.sub.3 N OCH.sub.3 133-135      188 H H H       ##STR172##       OH H N CH COCH.sub.3 N OCH.sub.3 115-117      189 H H H CONHCH.sub.2 COOCH.sub.3 OH H N CH COCH.sub.3 N OCH.sub.3      97-99      193 H H H       ##STR173##       OH H N CH COCH.sub.3 N OCH.sub.3 oil NMR      196 H H H       ##STR174##       OH H N CH COCH.sub.3 N OCH.sub.3 oil NMR      199 H H H COOH OH H N CH COCH.sub.3 N OCH.sub.3      200 H H H       ##STR175##       OH H N CH COCH.sub.3 N OCH.sub.3 144-146      201 H H H       ##STR176##       OH H N CH COCH.sub.3 N OCH.sub.3 oil NMR      207 H H H CONH.sub.2 dichloro- H N CH COCH.sub.3 N OCH.sub.3 118-119                acetoxy      209 H H H       ##STR177##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      210 H H H       ##STR178##       OH H N CH COCH.sub.3 N OCH.sub.3 119-121      211 H H H       ##STR179##       OH H N CH COCH.sub.3 N OCH.sub.3 125-127      212 H H H       ##STR180##       OH H N CH COCH.sub.3 N OCH.sub.3 oil NMR      213 H H H       ##STR181##       OH H N CH COCH.sub.3 N OCH.sub.3 oil NMR      214 H H H       ##STR182##       OH H N CH COCH.sub.3 N OCH.sub.3 oil NMR      215 H H H       ##STR183##       OH H N CH COCH.sub.3 N OCH.sub.3 119-120      217 H H H       ##STR184##       OH H N CH COCH.sub.3 N OCH.sub.3 182-183      221 H H H       ##STR185##       OH H N CH COCH.sub.3 N OCH.sub.3 105-106      223 H H H       ##STR186##       OH H N CH COCH.sub.3 N OCH.sub.3 130-131      224 H H H       ##STR187##       OH H N CH COCH.sub.3 N OCH.sub.3 149-150      225 H H H       ##STR188##       OH H N CH COCH.sub.3 N OCH.sub.3 98-100      226 H H H       ##STR189##       OH H N CH COCH.sub.3 N OCH.sub.3 40-42      227 H H H       ##STR190##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      229 H H H       ##STR191##       OH H N CH COCH.sub.3 N OCH.sub.3 121-123      230 H H H       ##STR192##       OH H N CH COCH.sub.3 N OCH.sub.3 130-132      231 H H H       ##STR193##       OH H N CH COCH.sub.3 N OCH.sub.3 138-140      232 H H H       ##STR194##       OH H N CH COCH.sub.3 N OCH.sub.3 152-154      233 H H H CONHC.sub.3 H.sub.6 N(CH.sub.3).sub.2 OH H N CH COCH.sub.3 N      OCH.sub.3 NMR       234 H H H CONHC.sub.2 H.sub.4 N(C.sub.2 H.sub.5).sub.2 OH H N CH      COCH.sub.3 N OCH.sub.3 NMR       241 H H H COOH OH "H1" N CH COCH.sub.3 N OCH.sub.3 Li.sup.+ salt                          158-160      245 H H H       ##STR195##       OH H N CH COCH.sub.3 N OCH.sub.3 150-154      246 H H H       ##STR196##       OH H N CH COCH.sub.3 N OCH.sub.3 133-134      252 H H H       ##STR197##       OH H N CH COCH.sub.3 N OCH.sub.3 150-151      255 H H H       ##STR198##       OH H N CH COCH.sub.3 N OCH.sub.3 52-54      257 H H H       ##STR199##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      259 H H H CONHC.sub.8 H.sub.17 OH H N CH COCH.sub.3 N OCH.sub.3 54-56      271 H H H       ##STR200##       OH N CH COCH.sub.3  N OCH.sub.3 137-138                                                                               2      72 H H H COOH O N CH COCH.sub.3 N OCH.sub.3 Li.sup.+       salt                            210 (decomp)      273 H H H       ##STR201##       O N CH COCH.sub.3 N OCH.sub.3 147-149       275 H H H       ##STR202##       OH H N CH COCH.sub.3 N OCH.sub.3 158-160                                                                               2      76 H H H COOH O N CH COCH.sub.3 N OCH.sub.3 Na.sup.+       salt                            195 (decomp)                  K.sup.+       salt                                                             (255      decomp)       278 H H H CONHC.sub.9 H.sub.19 OH H N CH COCH.sub.3 N OCH.sub.3 45-47         279 H H H CONHC.sub.10 H.sub.21 OH H N CH COCH.sub.3 N OCH.sub.3      49-51      280 H H H       ##STR203##       OH H N CH COCH.sub.3 N OCH.sub.3 58-62      282 H H H CONHCH.sub.2 iPr OH H N CH COCH.sub.3 N OCH.sub.3 103-105            283 H H H CONHCH.sub.2 CH(OCH.sub.3).sub.2 OH H N CH COCH.sub.3 N      OCH.sub.3 NMR       284 H H H CONHC(CH.sub.3).sub.2 CCH OH H N CH COCH.sub.3 N OCH.sub.3      NMR       285 H H H CONHC.sub.4 H.sub.9 OH H N CH COCH.sub.3 N OCH.sub.3 NMR            286 H H H CONHCHCH.sub.2       OCH.sub.3 OH H N CH COCH.sub.3 N OCH.sub.3 NMR           CH.sub.3      288 H H H       ##STR204##       OH H N CH COCH.sub.3 N OCH.sub.3 182-184      289 H H H       ##STR205##       OH H N CH COCH.sub.3 N OCH.sub.3 181-183      290 H H H       ##STR206##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      291 H H H CONHC.sub.6 H.sub.12 N(CH.sub.3).sub.2 OH H N CH COCH.sub.3 N      OCH.sub.3 NMR       292 H H H CONHC.sub.4 H.sub.8 N(CH.sub.3).sub.2 OH H N CH COCH.sub.3 N      OCH.sub.3 NMR      293 H H H       ##STR207##       OH H N CH COCH.sub.3 N OCH.sub.3 131-132      294 H H H       ##STR208##       OH H N CH COCH.sub.3 N OCH.sub.3 124-126      295 H H H       ##STR209##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      296 H H H       ##STR210##       OH H N CH COCH.sub.3 N OCH.sub.3 88-90      297 H H H       ##STR211##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      298 H H H       ##STR212##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      303 H H H       ##STR213##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      304 H H H       ##STR214##       OH H N CH COCH.sub.3 N OCH.sub.3 54-56      305 H H H       ##STR215##       OH H N CH COCH.sub.3 N OCH.sub.3 D(+) 64-68L(-) NMR      309 H H H       ##STR216##       OH H N CH COCH.sub.3 N OCH.sub.3 133-134      310 H H H       ##STR217##       OH H N CH COCH.sub.3 N OCH.sub.3 102-104      311 H H H       ##STR218##       OH H N CH COCH.sub.3 N OCH.sub.3 122-123      312 H H H       ##STR219##       OH H N CH COCH.sub.3 N OCH.sub.3 126-128      313 H H H       ##STR220##       OH H N CH COCH.sub.3 N OCH 106-108       318 H H H COOH OH H N CH COCH.sub.3 N CH.sub.3 Li.sup.+       salt                         185-188 (decomp)       322 H H H COOH OH H N CH CCH.sub.3 N CH.sub.3 Li.sup.+       salt                          >195 (decomp)       323 H H H COOH OH H N CH COCH.sub.3 N H Li.sup.+       salt                                >225 (decomp)       324 H H H COOH OH H N CH COCH.sub.3 N OC.sub.2 H.sub.5 Li.sup.+ salt                      195 (decomp)       325 H H H COOH OH H N CH COCH.sub.3 N Cl      327 H H H       ##STR221##       H H N CH COCH.sub.3 N OCH.sub.3 96-98       328 H H H       ##STR222##       O N CH COCH.sub.3 N OCH.sub.3 114-116      329 H H H       ##STR223##       O N CH COCH.sub.3 N OCH.sub.3 146-148      379 H H H CON(C.sub.2 H.sub.5).sub.2 O N CH COCH.sub.3 N OCH.sub.3      109-111       380 H H H CON(C.sub.2 H.sub.5).sub.2 OH H N CH COCH.sub.3 N OCH.sub.3         381 H H H CON(iC.sub.3 H.sub.7).sub.2 O N CH COCH.sub.3 N OCH.sub.3      146-148       382 H H H CON(iC.sub.3 H.sub.7).sub.2 OH H N CH COCH.sub.3 N OCH.sub.3       383 H H H       ##STR224##       O N CH COCH.sub.3 N OCH.sub.3       384 H H H       ##STR225##       OH H N CH COCH.sub.3 N OCH.sub.3                                                                               3      85 H H H CON(CH.sub.3).sub.2 O N CH COCH.sub.3 N OCH.sub.3 121-123             386 H H H CON(CH.sub.3).sub.2 OH H N CH COCH.sub.3 N OCH.sub.3       387 H H H       ##STR226##       O N CH COCH.sub.3 N OCH.sub.3       388 H H H       ##STR227##       OH H N CH COCH.sub.3 N OCH.sub.3       389 H H H       ##STR228##       O N CH COCH.sub.3 N OCH.sub.3 131-133       390 H H H       ##STR229##       OH H N CH COCH.sub.3 N OCH.sub.3       391 H H H       ##STR230##       O N CH COCH.sub.3 N OCH.sub.3       392 H H H       ##STR231##       OH H N CH COCH.sub.3 N OCH.sub.3       393 H H H       ##STR232##       O N CH COCH.sub.3 N OCH.sub.3 NMR       394 H H H       ##STR233##       OH H N CH COCH.sub.3 N OCH.sub.3       395 H H H       ##STR234##       O N CH COCH.sub.3 N OCH.sub.3 oil NMR       396 H H H       ##STR235##       OH H N CH COCH.sub.3 N OCH.sub.3       397 H H H       ##STR236##       O N CH COCH.sub.3 N OCH.sub.3       398 H H H       ##STR237##       OH H N CH COCH.sub.3 N OCH.sub.3       399 H H H       ##STR238##       O N CH COCH.sub.3 N OCH.sub.3       400 H H H       ##STR239##       OH H N CH COCH.sub.3 N OCH.sub.3       401 H H H       ##STR240##       O N CH COCH.sub.3 N OCH.sub.3       402 H H H       ##STR241##       OH H N CH COCH.sub.3 N OCH.sub.3       403 H H H       ##STR242##       O N CH COCH.sub.3 N OCH.sub.3 131-133       404 H H H       ##STR243##       OH H N CH COCH.sub.3 N OCH.sub.3       405 H H H       ##STR244##       O N CH COCH.sub.3 N OCH.sub.3 143-145       406 H H H       ##STR245##       OH H N CH COCH.sub.3 N OCH.sub.3      407 H H H       ##STR246##       OH H N CH COCH.sub.3 N OCH.sub.3 gum NMR      411 H H H CONHC.sub.2 H.sub.4 S(n)C.sub.4 H.sub.9 OH H N CH COCH.sub.3 N      OCH.sub.3 gum NMR       413 H H H CONCH.sub.2 CCH O N CH COCH.sub.3 N OCH.sub.3 gum NMR                   CH.sub.3       428 H H H CONHSC.sub.4 H.sub.9 OH H N CH COCH.sub.3 N OCH.sub.3 NMR      (racemate)       432 H H R CONHnC.sub.5 H.sub.11 OH H N CH COCH.sub.3 N OCH.sub.3 NMR          433 H H H CONHC.sub.7 H.sub.15 OH H N CH COCH.sub.3 N OCH.sub.3 NMR      434 H H H       ##STR247##       OH H N CH COCH.sub.3 N OCH.sub.3 143-145      435 H H H CONHCHC.sub.2 H.sub.5 OH H N CH COCH.sub.3 N OCH.sub.3 NMR               COOCH.sub.3       436 H H H CONH(s)C.sub.4 H.sub.9 OH H N CH COCH.sub.3 N OCH.sub.3 NMR      (both S(+) and                   R-(-) forms)       437 H H R CONHCH.sub.2       CCH OH H N CH CCH.sub.3 N OCH.sub.3 NMR       438 H H H       ##STR248##       OH N CH COCH.sub.3 N OCH.sub.3 139-141       439 H H H       ##STR249##       OH H N CH COCH.sub.3 N OCH.sub.3 143-144      440 H H H       ##STR250##       OH H N CH COCH.sub.3 N OCH.sub.3 133-134       441 H H H       ##STR251##       O N CH COCH.sub.3 N OCH.sub.3 117-120       442 H H H       ##STR252##       OH H N CH COCH.sub.3 N OCH.sub.3 127-128      443 H H H       ##STR253##       OH H N CH COCH.sub.3 N OCH.sub.3 138-140      444 H H H       ##STR254##       OH H H CH COCH.sub.3 N OCH.sub.3 152-153      445 H H H       ##STR255##       OH H N CH COCH.sub.3 N OCH.sub.3 108-110      446 H H H       ##STR256##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      447 H H H       ##STR257##       OH H N CH COCH.sub.3 N OCH.sub.3 130-131      449 H H H       ##STR258##       OH H N CH COCH.sub.3 N OCH.sub.3 116-117      450 H H H       ##STR259##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      453 H H H       ##STR260##       OH H N CH COCH.sub.3 N OCH.sub.3 100-102                                                                               4      54 H H H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3 N.sup.+ iC.sub.3      H.sub.7 salt                  201-203       455 H H H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.2 N.sup.+       (CH.sub.3).sub.2 salt                  183-185      456 H H H       ##STR261##       O N CH COCH.sub.3 N OCH.sub.3 115-116      457 H H H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.2 N.sup.+ (iC.sub.3      H.sub.7).sub.2 salt                  185-187       458 H H H CON-allyl O N CH COCH.sub.3 N OCH.sub.3 NMR           CH.sub.3       462 H H H       ##STR262##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      463 H H H       ##STR263##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR                                                                               4      64 H H H COOH O N CH COCH.sub.3 N OCH.sub.3 diCa.sup.++       salt                         >240       465 H H H COOH O N CH COCH.sub.3 N OCH.sub.3 diMg.sup.++       salt                       >240       466 H H H COOH O N CH COCH.sub.3 N OCH.sub.3 diAl.sup.++ OH salt                         >250      467 H H H       ##STR264##       O N CH COCH.sub.3 N OCH.sub.3 148-150       468 H H H       ##STR265##       OH H N CH COCH.sub.3 N OCH.sub.3 125-126      469 H H H       ##STR266##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      470 H H H       ##STR267##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      471 H H H       ##STR268##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      472 H H H       ##STR269##       OH H N CH COCH.sub.3 N OCH.sub.3 137-138      473 H H H       ##STR270##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      474 H H H       ##STR271##       OH H N CH COCH.sub.3 N OCH.sub.3 156-159      475 H H H       ##STR272##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      482 H H H COOH OH H N CH COCH.sub.3 N OCH.sub.3       ##STR273##      483 H H H COOH OH H N CH COCH.sub.3 N OCH.sub.3 H.sub.3 N.sup.+ C.sub.6      H.sub.13 salt                   NMR      484 H H H       ##STR274##       OH H N CH COCH.sub.3 N OCH.sub.3 113-115      485 H H H       ##STR275##       OH H N CH COCH.sub.3 N OCH.sub.3 147-148                                                                               4      87 H H H COOH O N CH COCH.sub.3 N OCH.sub.3 H.sub.3 N.sup.+ C.sub.6      H.sub.13 salt                  165-167      488 H H H COOH O N CH COCH.sub.3 N OCH.sub.3       ##STR276##       490 H H H       ##STR277##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      491 H H H       ##STR278##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR       492 H H H COOH O N OH COCH.sub.3 N OCH.sub.3 Al.sup.+ (OH).sub.2 salt                    >250       493 H H H COOH O N OH COCH.sub.3 N OCH.sub.3 Al.sup.++ OH/Phe.sup.-      salt                  >250      494 H H H       ##STR279##       O N CH COCH.sub.3 N OCH.sub.3 59-61       495 H H H       ##STR280##       OH H N CH COCH.sub.3 N OCH.sub.3 148-150       496 H H H       ##STR281##       O N CH COCH.sub.3 N OCH.sub.3 NMR      497 H H H       ##STR282##       O N CH COCH.sub.3 N OCH.sub.3 NMR       498 H H H       ##STR283##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR       500 H H H       ##STR284##       O N CH COCH.sub.3 N OCH.sub.3 NMR      501 H H H       ##STR285##       O N CH COCH.sub.3 N OCH.sub.3 NMR       505 H H H CONHCH.sub.2 CH.sub.2 OH OH H N CH COCH.sub.3 N OCH.sub.3 NMR      506 H H H       ##STR286##       OH H N CH COCH N OCH.sub.3 NMR                                                                               5      07 H H H CON(C.sub.3 H.sub.7).sub.2 O N CH COCH.sub.3 N OCH.sub.3      106-108      508 H H H       ##STR287##       O N CH COCH.sub.3 N OCH.sub.3 NMR      509 H H H       ##STR288##       O N CH COCH.sub.3 N OCH.sub.3 NMR       510 H H H       ##STR289##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      513 H H H       ##STR290##       OH H N CH COCH.sub.3 N OCH.sub.3 115-117      514 H H H       ##STR291##       OH H N CH COCH.sub.3 N OCH.sub.3 94-97      515 H H H       ##STR292##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      516 H H H       ##STR293##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      517 H H H       ##STR294##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      519 H H H       ##STR295##       OH H N CH COCH.sub.3 N OCH.sub.3 NMR      520 H H H       ##STR296##       OH H N CH COCH.sub.3 N OCH.sub.3 94-96       521 H H H       ##STR297##       O N CH COCH.sub.3 N OCH.sub.3 78-79      522 H H H       ##STR298##       O N CH COCH.sub.3 N OCH.sub.3 94-96      427 H H H       ##STR299##       O N CH COCH.sub.3 N OCH.sub.3 131-133      499 H H H       ##STR300##       O N CH COCH.sub.3 N OCH.sub.3 116-118                                                                               5      46 H H H CONHC.sub.2 H.sub.5 OH H N CH COCH.sub.3 N OCH.sub.3 48-50                                                                          558      H H H       ##STR301##       OH H N CH COCH.sub.3 N OCH.sub.3 108-110      562 H H 4-CH.sub.3 COOH OH H N CH COCH.sub.3 N OCH.sub.3 Li.sup.+ salt                     nmr       569 H H H       ##STR302##       O N CH COCH.sub.3 N OCH.sub.3 136-138      571 H H H       ##STR303##       O N CH COCH.sub.3 N OCH.sub.3 NMR      573 H H 4-OCH.sub.3 COOH O N CH COCH.sub.3 N OCH.sub.3 202-204       574 H H 4-OCH.sub.3 COOH O N CH COCH.sub.3 N OCH.sub.3 Li.sup.+ salt                     200-210      575 H H H       ##STR304##       O N CH COCH.sub.3 N OCH.sub.3 122-124      576 H H H       ##STR305##       O N CH COCH.sub.3 N OCH.sub.3 128-131      579 H H H       ##STR306##       O N CH COCH.sub.3 N OCH.sub.3 118-121      584 H H H       ##STR307##       O N CH COCH.sub.3 N OCH.sub.3 168-171      598 H H H       ##STR308##       O N CH COCH.sub.3 N OCH.sub.3 150-152      602 H H H       ##STR309##       O N CH COCH.sub.3 N OCH.sub.3 152-154      603 H H H       ##STR310##       O N CH COCH.sub.3 N OCH.sub.3 90-93      609 H H H       ##STR311##       O N CH COCH.sub.3 N OCH.sub.3 167-170      622 H H H COOsC.sub.4       H.sub.9 O N CH COCH.sub.3 N OCH.sub.3 NMR           625 H H H COOnC.sub.      4       H.sub.9 O N CH COCH.sub.3 N OCH.sub.3 NMR      626 H H H COOiC.sub.4 H.sub.9 O N CH COCH.sub.3 N OCH.sub.3 111-113                                                                          632      H H H       ##STR312##       OH N CH COCH.sub.3 N OCH.sub.3 122-127       633 H H H       ##STR313##       OH N CH COCH.sub.3 N OCH.sub.3 142-144       634 H H H       ##STR314##       OH N CH COCH.sub.3 N OCH.sub.3 156-158      (64: Lithium salt m.p. >250°; sodium salt m.p. >190°      (decomp); potassium salt m.p. >230°) (decomp)      Phe = Phenalanine anion

                                      TABLE F                                      __________________________________________________________________________      ##STR315##                                                                    Cpd #                                                                              AA                  X  Y    m.p.                                           __________________________________________________________________________      90                                                                                 ##STR316##         H  H    123-125                                        331                                                                                 ##STR317##         O                                                      332 "                   OH H                                                   333                                                                                 ##STR318##         O                                                      334 "                   OH H                                                   335                                                                                 ##STR319##         O                                                      336 "                   OH H                                                   337                                                                                 ##STR320##         O                                                      338 "                   OH H                                                   339                                                                                 ##STR321##         O                                                      340 "                   OH H                                                   341                                                                                 ##STR322##         O                                                      342 "                   OH H                                                   343                                                                                 ##STR323##         O                                                      344 "                   OH H                                                   345                                                                                 ##STR324##         O                                                      346 "                   OH H                                                   347                                                                                 ##STR325##         O                                                      348 "                   OH H                                                   349                                                                                 ##STR326##         O                                                      350 "                   OH H                                                   351                                                                                 ##STR327##         O                                                      352 "                   OH H                                                   353                                                                                 ##STR328##         O                                                      354 "                   OH H                                                   355                                                                                 ##STR329##         O                                                      356 "                   OH H                                                   357                                                                                 ##STR330##         O                                                      358 "                   OH H                                                   359                                                                                 ##STR331##         O                                                      360 "                   OH H                                                   361                                                                                 ##STR332##         O                                                      362 "                   OH H                                                   363                                                                                 ##STR333##         O                                                      364 "                   OH H                                                   365                                                                                 ##STR334##         O                                                      366 "                   OH H                                                   367                                                                                 ##STR335##         O                                                      368 "                   OH H                                                   369                                                                                 ##STR336##         O                                                      370 "                   OH H                                                   371                                                                                 ##STR337##         O                                                      372 "                   OH H                                                   373                                                                                 ##STR338##         O                                                      374 "                   OH H                                                   375                                                                                 ##STR339##         O                                                      376 "                   OH H                                                   377                                                                                 ##STR340##         O                                                      378 "                   OH H                                                   410                                                                                 ##STR341##         H  H    122-123                                        412 "                   H  O(t)C.sub.4 H.sub.9                                                                 gum NMR                                        424 "                   OH H    130-131                                        429 "                   O       NMR                                            430                                                                                 ##STR342##         H  O(t)C.sub.4 H.sub.9                                                                 NMR                                            431 "                   OH H    NMR                                            448                                                                                 ##STR343##         OH H    NMR                                            451                                                                                 ##STR344##         OH H    143-144                                        511                                                                                 ##STR345##         H  H    NMR                                            512 "                   H  O(t)C.sub.4 H.sub.9                                                                 NMR                                            513                                                                                 ##STR346##         H  H    92-93                                          514 "                   O       140-142                                        515                                                                                 ##STR347##         H  H    177-179                                        530                                                                                 ##STR348##         H  H    NMR                                            564                                                                                 ##STR349##         O       decompose 270                                  565                                                                                 ##STR350##            CN   155-158                                        601                                                                                 ##STR351##            OH   124-126                                        635                                                                                 ##STR352##         H  H    92-94                                          __________________________________________________________________________

Compounds of Table F wherein COOH is replaced by other meanings of R as listed in Tables C, D and E above for R may be prepared analogously.

NMR data [¹ H nmr (CDCl₃)

    ______________________________________                                         Cpd No                                                                         ______________________________________                                          41    δ: 3.95(s, 6H, OCH.sub.3), 5.95(s, 1H, pyrimidine H),                    6.45(s,                                                                        1H, OCH), 7.7-9.1(m, 3H, pyridine H).                                    44    δ: 1.32(t, 3H, CH.sub.3), 2.87(q, 2H, CH.sub.2), 4.05(s,                 6H,                                                                            OCH.sub.3), 6.3(s, 1H, OCH), 7.82(d, 1H, arom.), 8.72(d,                       1H, arom.).                                                              46    δ: 1.32(t, 3H, CH.sub.3), 2.85(q, 2H, CH.sub.2), 3.87(s,                 6H,                                                                            OCH.sub.3), 5.97(s, 1H, pyrimidine H), 6.32(s, 1H, OCH),                       8.08(d, 1H, pyridine H), 8.71(s, 1H, pyridine H).                        48    δ: 1.25(s, 6H, CH.sub.3), 3.85(s, 6H, OCH.sub.3), 3.95(2H,               OCH.sub.3), 4.65(s, 2H, CH.sub.2), 5.85(s, 1H,                                 pyrimidine H), 7.2-8.0(4H, aromatic).                                    49    δ: 1.00(s, 6H, CH.sub.3), 3.65 and 3.75(d of d, 2H,                      OCH.sub.2), 6.05(s, 1H, pyrimidine H),                                         7.2-8.1(4H, aromatic H).                                                 54    δ: 2.9(s, 3H, CH.sub.3 N), 3.10(s, 3H, CH.sub.3 O),                      3.90(s, 6H, OCH.sub.3), 6.10(s, 1H, pyrimidine H),                             7.2-7.9(3H, aromatic H).                                                 61    δ: 1.24(s, 6H, CH.sub.3), 3.98(s, 2H, CH.sub.2 O),                       4.74(s, 2H, CH.sub.2), 7.16(s, 1H, pyrimidine H).                        65    δ: 3.96(s, 6H, OCH.sub.3), 5.96(s, 1H, pyrimidine H),                    6.32(s, 1H, OCH), 7.27(d, 1H, thienyl H), 7.85(d, 1H,                          thienyl H).                                                              66    δ: 408(s, 6H, OCH.sub.3), 6.27(s, 1H, OCH), 7.18(s, 1H,                  thienyl H), 7.95(d, 1H, thienyl H).                                      76    δ: 1.63(t, 3H, C H.sub.3), 3.91(s, 6H,                                   OCH.sub.3), 4.1(q, 2H, OCH.sub.2), 6.08(s,                                     1H, pyrimidine H), 7.2-7.8(m, 3H, aromatic H).                           83    δ: 3.85(s, 6H, OCH.sub.3), 4.58(d, 2H, NCH.sub.3),                       5.30(s, 1H, OH), 5.80(s, 1H, pyrimidine H),                                    6.82(s, 1H, OCH), 7.25(s, 5H, aromatic), 7.40(dd,                              1H, pyridine), 7.98(dd, 1H, pyridine), 8.45(dd,                                1H, pyridine), 8.70(s, 1H, NH).                                          84    δ: 3.85(s, 6H, OCH.sub.3), 4.05(t, 2H, NCH.sub.2),                       5.0-5.45(m, 3H, CH═CH.sub.2), 5.85(s,                                      1H, pyrimidine), 6.80(s, 1H, OCH), 7.2-8.6(m,                                  3H, pyridine).                                                           86    δ: 3.85(s, OCH.sub.3), 5.37(s, OCH.sub.2 Ar), 5.85(s,                    pyrimidine), 6.80(s, OCH), 7.2-8.2(m,                                          aromatic), mixture with cpd. 40.                                         88    δ: 4.00(s, 3H, OCH.sub.3), 5.50(s, 2H, OCH.sub.2),                       6.05(s, 1H, pyrimidine H), 6.27(s,                                             1H, OCH) 7.1-7.7(m, 8H, aromatic H).                                     95    δ: 3.85(s, 6H, OCH.sub.3), 5.42(s, 2H, OCH.sub.2),                       6.05(s, 1H, pyrimidine), 6.42(s, 1H, OCH),                                     7.25(s, 5H, aromatic), 7.30(dd, 1H, pyridine),                                 7.98(dd, 1H, pyridine), 8.90(dd, 1H, pyridine).                          97    δ: 3.80(s, 6H, OCH.sub.3), 5.35(s, 2H, OCH.sub.2 Ar),                    5.85(s, 1H, pyrimidine), 6.65(s, 1H, OCH),                                     7.15-8.6(m, 8H, aromatic), mixture with cpd. 40.                        107    δ: 1.92(s, 3H, C.tbd.CCH.sub.3), 3.98(s, 6H, OCH.sub.3),                 4.92(s, 2H, OCH.sub.2), 6.07(s, 1H, pyrimidine),                               6.58(s, 1H, OCH), 7.71(dd, 1H, pyridine), 8.20                                 (dd, 1H, pyridine), 8.90(dd, 1H, pyridine).                             110    δ: 0.91(t, 3H, CH.sub.3), 1.53(m, 2H, CH.sub.2) 3.37(m,                  2H, CH.sub.2), 3.81(s, 6H, OCH.sub.3), 4.50(m,                                 3H, OH and NCH.sub.2), 5.82(s, 1H, pyrimidine),                                6.72(s, 1H, OCH), 7.37(dd, 1H, pyridine), 7.95(dd,                             1H, pyridine), 8.45(dd, 1H, pyridine).                                  112    δ: 1.22(d, 6H, CH.sub.3), 3.81(s, 6H, OCH.sub.3), 4.20(m,                1H, NCH), 5.85(s, 1H, pyrimidine), 6.71(s, 1H,                                 OCH), 7.38(dd, 1H, pyridine), 7.92(dd, 1H,                                     pyridine), 8.25(s, 1H, NH), 8.47(dd, 1H, pyridine).                     119    δ: 3.05(d, 3H, NCH.sub.3), 3.94(s, 6H, OCH.sub.3),                       5.20(s, 1H, OH), 5.75(s, 1H, pyrimidine), 5.98(s,                              1H, OCH), 7.26(d, 1H, pyridine H), 7.82(q, 1H,                                 NH), 8.28(d, 1H, pyridine H).                                           127    δ: 3.75(s, 6H, OCH.sub.3), 4.05(t, 2H, NCH.sub.2),                       5.05-5.5(m, 3H, CH═CH.sub.2),                                              5.85(s, 1H, pyrimidine), 7.2-8.6(m, 9H,                                        phenyl + OCH).                                                          128    δ: 2.20(s, 3H, CH.sub.3), 3.75(s, 6H, OCH.sub.3),                        4.10(t, 2H, NCH.sub.2), 5.0-6.6(m,                                             3H, CH═CH.sub.2), 5.85(s, 1H, pyrimidine),                                 7.2-8.6(m, 5H, pyridine + NH, OCH).                                     130    δ: 1.30(m, 15H, aliphatic), 2.26(m, 8H, aliphatic),                      3.36(m, 2H, NCH.sub.2), 3.83(s, 6H,                                            OCH.sub.3), 5.82(s, 1H, pyrimidine), 6.81(s,                                   1H, OCH), 7.38(dd, 1H, pyridine), 8.06(dd, 1H,                                 pyridine), 8.29(s, 1H, NH), 8.46(dd, 1H, pyridine).                     133    δ: 2.85(d, 3H, NCH.sub.3), 3.85(s, 6H, OCH.sub.3),                       4.10(t, 2H, NCH.sub.2), 5.0-6.0(m, 3H,                                         CH═CH.sub.2), 5.85(s, 1H, pyrimidine),                                     7.2-8.6(m, 4H, pyridine + OCH).                                         150    δ 0.96(t, 3H, CH.sub.3), 1.68(m, 2H,  CH.sub.2),                         3.50(m, 2H, NCH.sub.2), 3.93(s, 6H, OCH.sub.3),                                5.92(s, 1H, pyrimidine H), 6.17(d, 1H, OCH), 7.21(d of                         d, 1H, pyridine H), 8.07(dd, 1H, pyridine H), 8.57(dd,                         1H, pyridine H), 8.66(t, 1H, NH).                                       151    δ: 1.50(d, 3H, CH.sub.3), 3.82(s, 6H, OCH.sub.3), 5.21(m,                2H, NCH, OH), 5.81(s, 1H, pyrimidine), 6.85(s, 1H,                             OCH), 7.23(m, 6H, phenyl and pyridine), 7.89(dd, 1H,                           pyridine), 8.42(dd, 1H, pyridine), 8.62(s, 1H, NH).                     152    δ: 2.18(s, 3H, CH.sub.3), 3.89(s, 6H, OCH.sub.3),                        4.42(d, 2H, NCH.sub.2), 5.81(s, 1H, pyrimidine),                               6.85(s, 1H, OCH), 7.03(s, 4H, phenyl), 7.21(dd, 1H,                            pyridine), 7.91(dd, 1H, pyridine), 8.42(dd, 1H,                                pyridine), 8.51(s, 1H, NH).                                             171    δ: 1.24(t, 3H, CH.sub.3), 2.60(q, 2H, CH.sub.2), 3.86(s,                 6H, OCH.sub.3), 4.62(d, 2H, NCH.sub.2), 5.86(s,                                1H, pyrimidine H), 6.90(d, 1H, OCH), 7.0-8.54(m,                               7H, phenyl), 8.60(bs, 1H, NH).                                          174    δ: 3.83(s, 3H, OCH.sub.3), 3.90(s, 6H, OCH.sub.3),                       5.83(s, 1H, pyrimidine H), 6.60(d, 1H, OCH), 7.30(dd,                          1H, pyridine H), 8.23(dd, 1H, pyridine H), 8.70(dd,                            1H, pyridine H).                                                        177    δ: 2.20(s, 6H, CH.sub.3), 2.38(t, 2H, CH.sub.2 N),                       3.42(q, 2H, NCH.sub.2), 3.78(s, 6H, OCH.sub.3),                                4.88(br, 1H, NH) 5.75(s, 1H, pyrimidine), 6.61(s, 1H,                          OCH), 7.29(dd, 1H, pyridine), 7.80(dd, 1H, pyridine),                          8.34(dd, 1H, pyridine).                                                 178    δ: 3.85(s, 9H, OCH.sub.3), 3.95(s, 3H, OCH.sub.3),                       4.14(s, 2H, CH.sub.2), 5.82(s, 1H, pyrimidine H),                              6.90(d, 1H, pyridine H), 8.12(d, 1H, pyridine H).                       187    δ: 3.70(s, 9H, OCH.sub.3), 5.82(s, 1H, pyrimidine H),                    ;6.80(d, 1H, pyridine H), 8.10(d, 1H, pyridine H).                      193    δ: 1.00(d, 6H, CH.sub.3), 3.78(s, 3H, OCH.sub.3),                        3.85(s, 6H, OCH.sub.3), 4.72(q, 1H, CH), 5.50(d,                               2H, OH and NCH), 5.82(s, 1H, pyrimidine), 6.88(s,                              1H, OCH), 7.40(dd, 1H, pyridine), 7.98(dd, 1H,                                 pyridine), 8.52(dd, 1H, pyridine), 8.78(s, 1H, NH).                     196    δ: 3.78(s, 6H, OCH.sub.3), 4.70(d, 2H, NCH.sub.2),                       5.35(s, 1H, OH), 5.81(s, 1H, pyrimidine), 6.28(m,                              2H, furfuryl), 6.81(s, 1H, OCH), 7.30(m, 2H, furfuryl;                         pyridine), 7.98(dd, 1H, pyridine), 8.41(dd, 1H,                                pyridine), 8.67(s, 1H, NH).                                             201    δ: 1.87-2.04(m, 4H, CH.sub.2 and tetrahydrofuran),                       3.71-3.92(m, 9H, OCH.sub.3 and tetrahydro-                                     furan), 5.86-5.87(m, 2H, pyrimidine and OH),                                   6.74(d, 1H, OCH), 7.39(dd, 1H, pyridine), 7.88(dd,                             1H, pyridine), 8.48(dd, 1H, pyridine), 8.55(s, 1H, NH).                 206    δ: 2.22(s, 1H, CH.sub.3), 3.85(s, 6H, OCH.sub.3), 3.92(s,                3H, OCH.sub.3), 3.97(s, 3H, OCH.sub.3), 5.86(s,                                1H, pyrimdine H), 6.80(s, 1H, OCH), 7.10(d, 1H,                                pyridine H), 8.16(d, 1H, pyridine H).                                   209    δ: 3.63(t, 3H, OCH.sub.3), 3.74(s, 6H, OCH.sub.3),                       5.48-5.81(m, 4H, pyrimidine, OH, COCH),                                        6.88-7.42(m, 8H, phenyl, OCH, pyridine),                                       7.95(dd, 1H, pyridine), 8.46(dd, 1H, pyridine)                                 9.25(d, 1H, NH).                                                        212    δ: 3.85(s, 6H, OCH.sub.3), 4.41-4.52(m, 2H,                              NCH.sub.2), 5.21-5.72(d, s, 4H, NH.sub.2,                                      pyrimidine, OH), 6.61(s, 1H, OCH), 7.12-7.32(m,                                3H, pyridine, benzylsulfon), 7.71-7.80(m, 3H,                                  pyridine, benzylsulfon), 8.3(d, 1H, pyridine), 8.71(m,                         1H, NH).                                                                213    δ: 3.61(s, 6H, OCH.sub.3), 4.60(d, 2H, CH.sub.2, OH),                    4.90(s,                                                                        1H, OH) 5.72(s, 1H, pyrimidine), 6.72(s, 1H, OCH),                             7.16-8.41(m, 7H, pyridine), 9.12(s, 1H, NH).                            214    δ: 3.75(s, 6H, OCH.sub.3), 4.73(d, 2H, NCH.sub.2), 5.84(s,               1H,                                                                            pyrimidine), 6.86-6.96(m, 3H, OCH, thiophene), 7.15(d,                         1H, thiophene), 7.34(dd, Jcb=4.7, Jcd=7.9, 1H,                                 pyridine), 7.96(dd, Jdc=7.9, Jdb=1.5, 1H, pyridine)                            8.4(dd, Jbc=4.7, Jbd= 1.5, 1H, pyridine), 8.71(d,                              1H, NH).                                                                216    δ: 1.31(t, 3H, CH.sub.3), 2.62(s, 3H, CH.sub.3), 3.87(s,                 6H,                                                                            OCH.sub.3), 4.21(s, 2H, CH.sub.2), 4.40(q, 2H,                                 OCH.sub.2), 5.83(s, 1H, pyrimidine H), 7.13(d, 1H,                             pyridine H), 8.44(d, 1H, pyridine H).                                   218    δ: 284(3.08)(s, 3H, NCH.sub.3), 3.92(s, 6H, OCH.sub.3),                  4.50-                                                                          5.03(m, 2H, NCH.sub.2), 6.10(s, 1H, pyrimidine H),                             7.10-7.80(m, 7H, aromatic H).                                           227    δ: 1.50(m, 6H, CH.sub.2), 2.40(m, 6H, NCH.sub.2), 3.55(q,                2H,                                                                            NCH.sub.2), 3.80(s, 6H, OCH.sub.3), 5.85(s, 1H,                                pyrimidine H), 6.70(s, 1H, OCH), 7.15-8.60(m,                                  4H, 3 pyridine H + NH).                                                 233    δ: 1.80(q, 2H, CH.sub.2), 2.25(s, 6H, NCH.sub.3), 2.35(q,                2H,                                                                            NCH.sub.2), 3.45(q, 2H, NCH.sub.2), 3.80(s, 6H,                                CH.sub.3), 5.80(s, 1H, pyrimidine), 6.65(s, 1H,                                OCH), 7.15-850(m, 3H, pyridine).                                        234    δ: 1.00(t, 6H, CH.sub.3), 2.60(m, 6H, NCH.sub.2), 3.50(q,                2H,                                                                            NCH.sub.2), 3.92(s, 6H, O)CH.sub.3), 5.80(s, 1H,                               pyrimidine H), 6.80(s, 1H, OCH), 7.15-8.7(m, 3H,                               pyridine).                                                              236    δ: 1.37(t, 3H, CH.sub.3), 2.56(s, 3H, CH.sub.3), 3.87(s,                 6H,                                                                            OCH.sub.3), 4.43(q, 2H, OCH.sub.2), 5.87(s, 1H,                                pyrimidine H), 6.12(s, 1H, CHBr), 7.90(s, 1H, pyridine                         H), 8.56(d, 1H, pyridine H).                                            237    δ: 1.40(t, 3H, CH.sub.3), 3.87(s, 6H, OCH.sub.3), 4.43(q,                2H,                                                                            OCH.sub.2), 4.70(s, 2H, CH.sub.2 Br), 5.88(s, 1H,                              pyrimidine H), 6.23(s, 1H, CHBr), 8.07(d, 1H, pyridine                         H), 8.65(d, 1H, pyridine H).                                            238    δ: 1.37(t, 3H, CH.sub.3), 2.06(s, 3H, CH.sub.3), 3.88(s,                 6H,                                                                            OCH.sub.3), 4.40(q, 2H, OCH.sub.2), 5.28(s, 2H,                                OCH.sub.2), 5.87(s, 1H, pyrimidine H), 6.23(s, 1H,                             CHBr), 8.04(d, 1H, pyridine H), 8.64(d, 1H, pyridine                           H).                                                                     257    δ: 3.82(s, 6H, OCH.sub.3), 4.06(s, 2H, NCH.sub.2), 5.08(s,               1H,                                                                            OH), 5.43(s, 1H, NH), 5.87(s, 1H, OCH), 6.82(s, 1H,                            pyrimidine), 7.32-7.38(m, 6H, pyridine; phenyl),                               7.88(dd, 1H, pyridine), 8.45(dd, 1H, pyridine),                                9.55(s, 1H, NH).                                                        264    δ: 0.8-1.9(br s, 25H, aliphatic), 3.85-3.90(s, 6H,                       OCH.sub.3),                                                                    6.15(s, 1H, ArH, pyrimidine), 7.4(s, 2H, ArH).                          277    δ: 0.90(t, 3H, CH.sub.3), 1.2-1.7(m, 4H, aliphatic),                     3.95(s,                                                                        6H, OCH.sub.3), 4.08(t, 2H, OCH.sub.2),                                        6.15(s, 1H, pyrimidine H), 7.5-7.7(m, 3H,                                      aromatic).                                                              281    δ: 0.90(t, 3H, CH.sub.3), 1.3(m, 4H, aliphatic), 1.6(m, 2H,              aliphatic), 3.95(s, 6H, OCH.sub.3), 4.08(t,                                    2H, OCH.sub.2), 6.15(s, 1H, pyrimidine H),                                     7.4-7.7(m, 3H, aromatic).                                               283    δ: 3.40(s, 6H, OCH.sub.3), 3.43(m, 2H, NCH.sub.2), 3.82(s,               6H, OCH.sub.3), 4.47(t, 1H, CH), 5.75(s, 1H,                                   OH), 5.86(s, 1H, pyrimidine), 6.77(s, 1H, OCH),                                7.41(dd, 1H, pyridine), 7.96(dd, 1H, pyridine),                                8.47(m, 2H, NH, pyridine).                                              284    δ: 1.75(s, 6H, CH.sub.3), 2.31(s, 1H, C═CH), 3.85(s,                 6H,                                                                            OCH.sub.3), 5.62(d, 1H, OH), 5.85(s, 1H,                                       pyrimidine), 6.85(d, 1H, OCH), 7.45(dd, 1H,                                    pyridine), 7.95(dd, 1H, pyridine), 8.44-                                       8.45(m, 2H, NH, pyridine).                                              285    δ: 0.85(t, 3H, CH.sub.3), 1.48(m, 4H, CH.sub.2), 3.41(m,                 2H,                                                                            NCH.sub.2), 3.82(s, 6H, OCH.sub.3), 5.75(m,                                    2H, OH, pyrimidine), 6.66(d, 1H, OCH), 7.31(dd,                                1H, pyridine), 7.86(d, 1H, pyridine), 8.27(s, 1H,                              NH), 8.40(dd, 1H, pyridine).                                            286    δ: 1.28(t, 3H, CH.sub.3), 3.38-3.58(m, 4H, CH, CH.sub.3),                3.85(s, 6H, OCH.sub.3), 4.18-4,48(m, 2H, CH.sub.2),                            5.88(s, 1H, pyrimidine), 6.73(s, 1H, OCH), 7.53-                               8.42(m, 4H, pyridine, NH).                                              290    δ: 3.74(s, 9H, OCH.sub.3), 5.44(bs, 1H, OH), 5.73(s, 1H,                 pyrimidine), 6.62(bs, 1H, OCH), 6.9-8.6(m, aromatic,                           7H), 10.22(s, 1H, NH).                                                  291    δ: 1.40(m, 8H, CH.sub.2), 2,28(s, 6H, NCH.sub.3), 2.68(m,                2H, NCH.sub.2), 3.40(m, 2H, NCH.sub.2), 3.80(s,                                6H, OCH.sub.3), 5.80(s, 1H, pyrimidine), 6.70(s, 1H,                           OCH), 7.2-8.6(m, 4H, pyridine H + OH).                                  292    δ: 1.60(m, 4H, CH.sub.2), 2.25(s, 6H, NCH.sub.3), 2.25(m,                2H,                                                                            NCH.sub.2), 3.48(m, 2H, NCH.sub.2), 3.65(s, 6H,                                OCH.sub.3), 5.80(s, 1H, pyrimidine), 6.65(s, 1H,                               OCH), 7.2-8.6(m, 4H, pyridine + OH).                                    295    δ: 3.74(s, 6H, OCH.sub.3), 3.80(s, 6H, OCH.sub.3), 4.50(s,               2H,                                                                            NCH.sub.2), 5.84(s, 1H, pyrimidine), 6.5-                                      8.6(m, 8H, phenyl, OCH, NH).                                            297    δ: 3.65(s, 6H, OCH.sub.3), 3.77(s, 6H, OCH.sub.3), 4.50(s,               2H,                                                                            NCH.sub.2), 5.64(d, 1H, OH), 5.80(s, 1H,                                       pyrimidine), 6.25-6.60(m, 3H, phenyl), 6.8(d,                                  1H, OCH), 7.2-8.6(m, 3H, pyridine).                                     298    δ: 1.21(d, 3H, CH.sub.3), 3.26(m, 1H, CH), 3.61(m, 2H,                   CH.sub.2), 3.82(s, 6H, OCH.sub.3), 5.86(s,                                     1H, pyrimidine), 6.7(s, 1H, CH), 7.38(dd, 1H,                                  pyridine), 7.90(dd, 1H, pyridine), 8.43(dd, 1H,                                pyridine), 8.61(br, 1H, NH).                                            299    δ: 0.85(t, 3H, CH.sub.3), 1.2(m, 8H, aliphatic), 1.6(m, 2H,              aliphatic), 3.95(s, 6H, OCH.sub.3), 4.08(t, 2H,                                OCH.sub.2), 6.15(s, 1H, pyrimidine H), 7.4-7.7                                 (m, 3H, aromatic).                                                      300    δ: 0.90(t, 3H, CH.sub.3), 1.2(m, 10H, aliphatic), 1.6(m,                 2H,                                                                            aliphatic), 3.95(s, 6H, OCH.sub.3), 4.08(t, 2H,                                OCH.sub.3), 4.08(t, 2H, OCH.sub.2), 6.15(s, 1H,                                pyrimidine H), 7.4-7.7(m, 3H, phenyl).                                  303    δ: 3.80(s, 6H, OCH.sub.3), 3.90(d, 6H, OCH.sub.3), 5.45(d,               1H, OH), 5.80(s, 1H, pyrimidine), 6.85(s, 1H, OCH),                            7.0-8.6(m, 6H, phenyl), 10.2(s, 1H, NH).                                305L(-)                                                                               δ: 1.60(d, 3H, CH.sub.3), 3.75(2s, 6H, OCH.sub.3),                       5.25(m, 1H, OH), 5.75(s, 1H, pyrimidine), 6.75(d, 1H,                          OCH), 7.2-8.6(m, 8H, aromatic).                                         308    δ: 0.88(t, 3H, CH.sub.3), 1.25(bs, 18H, aliphatic), 1.6(m,               2H,                                                                            aliphatic), 3.95(s, 6H, OCH.sub.3), 4.07(t, 2H,                                O--CH.sub.2), 6.15(s, 1H, pyrimidine H),                                       7.55-7.7(m, 3H, aromatic).                                              330    δ: 1.05(m, 6H, NCH.sub.2 CH.sub.3), 1.27(s, 9H,                          C(CH.sub.3).sub.2),                                                            2.3(m, 4H, NCH.sub.2), 3.8(s, 6H, OCH.sub.3),                                  5.8(s, 1H, pyrimidine H), 5.9(s, 1H, CH--Ot-Bu),                               7.18(d of d, 1H, pyridine H), 7.45(d of d, 1H,                                 pyridine H), 8.6(d of d, 1H, pyridine H).                               393    δ: 0.86(d, 3H, CH.sub.3), 1.12-1.26(m, 8H, CH.sub.2),                    3.15(s, 3H, NCH.sub.3), 3.32(m, 2H, CH.sub.2),                                 3.93(s, 6H, OCH.sub.3), 6.14(s, 1H, pyrimidine),                               7.46(dd, Jca=4.8, Jcb=7.8, 1H, pyridine), 8.12(dd,                             Jba=1.3, Jbc=7.8, 1H, pyridine), 8.68(dd, Jab=                                 1.2, Jac=4.8).                                                          395    δ: 3.10(s, 3H, N--CH.sub.3), 3.86(s, 6H, OCH.sub.3),                     4.58(s, 2H, CH.sub.2), 6.06(s, 1H, pyrimidine),                                7.18-8.69(m, 8H, pyridine, phenyl).                                     407    δ: 3.18(m, 2H, CH.sub.2 S0, 3.65(m, 2H, CH.sub.2 N),                     3.95(s,                                                                        6H, OCH.sub.3), 5.85(s, 1H, pyrimidine), 6.80(s, 1H,                           OCH), 7.0-8.7(m, 8H, aromatic).                                         411    δ: 1.90(t, 3H, CH.sub.3), 1.55(m, 4H, CH.sub.2), 2.65(m,                 4H,                                                                            CH.sub.2 S), 3.62(m, 2H, CH.sub.2 N), 3.82(s, 6H,                              CH.sub.3 O), 5.90(s, 1H, pyrimidine), 6.75(s, OCH),                            7.2-8.65(m, 3H, pyridine).                                              412    δ: 1.37(s, 9H, tBuO), 3.30(s, 3H, CH.sub.3 N), 3.90(s, 6H,               CH.sub.3), 5.95(s, 1H, pyridimidine), 5.97(s, 1H,                              OCH), 6.5-6.7(m, 10H, aromatic).                                        413    δ: 2.23(s, 1H, C.tbd.CH), 3.12-3.23(d, 3H, N--CH.sub.3),                 3.93(s, 8H, OCH.sub.3, N--CH.sub.2 C═),                                    6.15(s, 1H, pyrimidine), 7.47-7.52(m, 1H, pyridine),                           8.14-8.17(m, 1H, pyridine), 8.69-8.71(t, 1H,                                   pyridine).                                                              4.28   δ: 0.71-1.80(m, 8H, alphatic), 3.02(s, 6H, OCH.sub.3),                   3.92-4.20(m, 1H, NCH), 5.82(s, 1H, pyrimidine), 6.67(s,                        1H, OCH), 7.20-8.50(m, 4H, pyridine + NH).                              429    δ: 3.38(s, 3H, NCH.sub.3), 4.02(s, 6H, OCH.sub.3), 6.20(s,               1H, pyrimidine), 6.63-7.90(m, 10H, aromatic).                           430    δ: 1.3(s, 9H, t-Bu), 3.4(s, 3H, N--CH.sub.3), 3.9(s, 6H,                 OCH.sub.3), 5.9(s, H, pyrimidine H0, 6.57(m, 2H, CH--O +                       thiophene H), 7.05(m, 6H, thiophene H, phenyl).                         431    δ: 3.46(s, 3H, N--CH.sub.3), 3.97(s, 6H, OCH.sub.3),                     5.2(d, 1H, OH), 5.87(s, 1H, pyrimidine H), 6.1(d, 1H,                          CH--O), 6.32(d, 1H, thiophene H), 6.75(d, 1H,                                  thiophene H), 7.05(m, 5H, phenyl).                                      432    δ: 0.92(t, 3H, CH.sub.3), 1.42(m, 6H, CH.sub.2), 3.42(m,                 2H, NCH.sub.2), 3.85(s, 6H, OCH.sub.3), 5.85(s,                                1H, pyrimidine), 6.72(d, 1H, OCH), 7.22-8.60(m,                                4H, pyridine + NH).                                                     433    δ: 0.90(t, 3H, CH.sub.3), 1.32(m, 10H, CH), 3.45(m, 2H,                  NCH.sub.2), 3.92(s, 6H, OCH.sub.3), 5.85(s, 1H,                                pyrimidine), 6.75(s, 1H, OCH), 7.2-8.6(m, 4H,                                  pyridine + NH).                                                         435    δ: 0.96(t, 3H, CH.sub.3), 1.92(m, 2H, CH.sub.2), 3.78(s,                 3H,                                                                            OCH.sub.3), 3.86(s, 6H, OCH.sub.3), 4.60(m, 1H,                                NCH), 5.86(s, 1H, pyrimidine), 6.86(d, 1H, OCH), 7.2-                          8.9(m, 4H, pyridine + NH).                                              436    (S)-(+)-amine δ: 0.76-1.74(m, 8H, CH.sub.3, CH.sub.2),                   3.86(s, 6H, OCH.sub.3), 4.06(m, 1H, NCH), 5.86(s, 1H,                          pyrimidine), 6.70(d, 1H, OCH), 7.60-8.60(m, 4H,                                pyridine NH).                                                           436    (R)-(-)-amine δ: 0.70-1.85(m, 8H, CH.sub.3, CH.sub.2),                   3.90(s, 6H, OCH.sub.3), 4.05(m, 1H, NCH), 5.85(s,                              1H, pyrimidine), 6.65(s, 1H, OCH), 7.20-8.60                                   (m, 4H, pyridine, NH).                                                  437    δ: 2.25(m, 1H, ═CH), 2.45(s, 3H, CH.sub.3), 3.80(s, 3H,              OCH.sub.3), 4.25(m, 2H, NCH.sub.2), 6.38(s, 1H,                                pyrimidine), 6.95(s, 1H, OCH), 7.25-8.65(m,                                    4H, pyrimidine, NH).                                                    446    δ: 1.45(t, 3H, CH.sub.3), 3.82(s, 6H, OCH.sub.3), 4.12(q,                2H,                                                                            OCH.sub.2), 5.42(d, 1H, OH), 5.88(s, 1H, pyrimidine),                          6.72(m, 1H, OCH), 7.00-8.65(m, 7H, phenyl, pyridine),                          10.32(s, 1H, NH).                                                       448    δ: 3.45(s, 3H, NCH.sub.3), 3.95(s, 6H, OCH.sub.3), 5.35(s,               1H,                                                                            OH), 5.95(s, 1H, pyrimidine), 6.15(s, 1H, OCH), 6.90-                          7.40(m, 5H, phenyl), 7.94(s, 1H, isothiazole).                          450    δ: 3.38(s, 3H, NCH.sub.3), 3.72(s, 6H, OCH.sub.3), 4.47(s,               2H,                                                                            CH.sub.2), 5.38(s, 1H, OH), 6.94-8.62(m,                                       8H, OCH, benzene, pyridine), 10.64(s, 1H, NH).                          458    δ: 3.10(s, 3H, N--CH.sub.3), 3.95(m, 8H, CH.sub.2,                       OCH.sub.3), 5.19(m, 1H, ═CH), 6.17(s, 1H,                                  pyrimidine), 7.49(dd, 1H pyridine), 8.16(dd, 1H,                               pyridine), 8.69(dd, 1H, pyridine).                                      462    δ: 3.40(s, 3H OCH.sub.3), 3.82(s, 6H, OCH.sub.3), 4.48(s,                2H,                                                                            CH.sub.3), 4.63(s, 2H, NCH.sub.2), 5.73(s, 1H,                                 OH), 5.88(s, 1H, pyrimidine), 6.80(s, 1H, OCH), 7.28-                          8.80(m, 8H, benzene, pyridine, NH).                                     463    δ: 3.83(s, 6H, OCH.sub.3), 4.43(d, 1H, OH), 5.75(s, 1H,                  pyrimidine), 6.75(s, 1H, OCH), 7.10-8.45(m, 7H,                                phenyl, pyridine), 8.70(t, 1H, NH).                                     469    δ: 3.80(s, 6H, OCH.sub.3), 3.90(d, 6H, OCH.sub.3), 5.60(s,               1H, OH), 5.85(s, 1H, pyrimidine), 6.35-8.70(m, 7H,                             OCH, pyridine, phenyl), 10.30(s, 1H, NH).                               470    δ: 1.10(t, 6H, CH.sub.3), 2.53(q, 4H, CH.sub.2), 3.75(s,                 6H,                                                                            OCH.sub.3), 5.80(s, 1H, pyrimidine), 5.90(d, 1H, OH),                          6.45(d, 1H, OCH), 7.00-8.60(m, 6H, phenyl, pyridine),                          9.78(s, 1H, NH).                                                        471    δ: 3.34(s, 3H, OCH.sub.3), 3.37(s, 6H, OCH.sub.3), 4.42(s,               2H,                                                                            OCH.sub.2), 4.63(d, 2H, NCH.sub.2), 5.74(d, 1H, OH),                           5.80(s, 1H, pyrimidine), 6.80(d, 1H, OCH), 7.22-8.50(M,                        7H, phenyl, pyrimidine), 8.65(t, 1H, NH).                               473    δ: 3.35(s, 3H, N--CH.sub.3), 3.95(s, 6H, OCH.sub.3),                     6.27(s,                                                                        1H, CH), 6.66(s, 1H, pyrimidine), 6.93-8.93(d, 8H,                             phenyl, pyridine).                                                      475    δ: 3.40(s, 3H, OCH.sub.3), 3.75(s, 6H, OCH.sub.3), 4.52(s,               2H,                                                                            CH.sub.2), 4.66(d, 2H, NCH.sub.2), 5.82(d, 1H, OH), 5.85(s,                    1H, pyrimidine), 6.76(d, 1H, OCH), 7.20-8.60(m, 7H,                            phenyl, pyridine), 8.85(t, 1H, NH).                                     482    δ: 2.20-2.70(m, 10H, NCH.sub.2, CH.sub.2), 3.40-3.80(m,                  4H, OCH.sub.2), 3.85(s, 6H, OCH.sub.3), 5.85(s, 1H,                            pyrimidine), 6.20(s, 1H, OCH), 7.15-8.70(m, 3H,                                pyridine).                                                              483    δ: 0.60-1.80(m, 11H, CH.sub.2, CH.sub.3), 2.60-3.00(m,                   2H, NCH.sub.2), 3.88(s, 6H, OCH.sub.3), 5.85(s, 1H,                            pyrimidine), 6.20(s, 1H, OCH), 7.00-8.70(m, 3H,                                pyridine).                                                              490    δ: 2.55(t, 1H, ═CH), 3.82(s, 6H, OCH.sub.3), 4.68(d,                 1H,                                                                            OCH.sub.2), 5.45(d, 1H, OH), 5.85(s, 1H, pyrimidine),                          6.90(d, 1H, OCH), 6.90-8.70(m, 7H, phenyl, pyridine),                          10.25(s, 1H, NH).                                                       491    δ: 2.55(t, 1H, ═CH), 3.80(s, 6H, OCH.sub.3), 5.42(d,                 1H,                                                                            OH), 5.84(s, 1H, pyrimidine), 6.80(m, 1H, OCH), 6.80-                          8.70(m, 7H, phenyl, pyridine), 10.40(s, 1H, NH).                        496    δ 3.19(s, 3H, N--CH.sub.3), 3.69(t, 2H, CH.sub.2),                       3.82(m, 2H, CH.sub.2), 3.94(s, 6H, OCH.sub.3),                                 6.17(s, 1H, pyrimidine), 7.55(dd, 1H, pyridine), 8.19                          (dd, 1H, pyridine), 8.61(dd, 1H, pyridine).                             497    δ: 0.89(t, 3H, CH.sub.3), 1.26(m, 4H, CH.sub.2), 3.14(s,                 3H, --NCH.sub.3), 3.34(m, 2H, CH.sub.2), 3.93(s,                               6H, OCH.sub.3), 6.15(s, 1H, pyrimidine), 7.46(dd, 1H,                          pyridine), 8.13(dd, 1H, pyridine), 8.68(dd, 1H,                                pyridine).                                                              498    δ: 0.70-1.70(m, 10H, CH.sub.2 CH.sub.3), 3.85(s, 6H,                     OCH.sub.3), 4.20(m, 1H, NCH), 5.85(s, 1H, pyrimidine),                         5.95(d, 1H, OH), 6.68(d, 1H, OCH), 7.25-8.65(m, 4H,                            pyridine, NH).                                                          500    δ: 2.30(s, 6H, N(CH.sub.3).sub.2), 3.19(s, 3H,                           N--CH.sub.3), 3.54(m, 4H, CH.sub.2), 3.94(s, 6H,                               OCH.sub.3), 6.16(s, 1H, pyrimidine), 7.48(dd, Jca=2.8,                         Jcb=4.8, 1H, pyridine), 8.15(dd, Jbc=4.8, Jba=1.5,                             1H, pyridine), 8.69(dd, Jca=2.8, Jab=1.5, 1H,                                  pyridine).                                                              501    δ: 3.16(s, 3H, NCH.sub.3), 3.19-3.27(m, 9H, OCH.sub.3,                   CH.sub.2, CH), 3.71(s, 6H, OCH.sub.3), 5.96(s, 1H,                             pyrimidine), 7.27-7.31(d, 1H, pyridine), 7.93-                                 7.96(d, 1H, pyridine), 8.46-8.50(d, 1H, pyridine).                      505    δ: 3.35-4.10(m, 6H, NCH.sub.2, OCH.sub.2, NH, OH), 3.80(s,               6H, OCH.sub.3), 5.75(d, 1H, OH), 5.80(s, 1H,                                   pyrimidine), 6.70(d, 1H, OCH), 7.20-8.30(m, 3H,                                pyridine), 8.60(m, 1H, NH).                                             506    δ: 1.00(m, 6H, CH.sub.3), 1.60(m, 3H, CH.sub.2, CH), 3.75-               4.38(m, 6H, NH, NCH, CH.sub.2 OH), 3.88(s, 6H,                                 OCH.sub.3), 5.90(s, 1H, pyrimidine), 6.76(s, 1H,                               OCH), 7.28-7.72(m, 4H, pyridine, NH).                                   508    δ: 3.27(s, 3H, NCH.sub.3), 3.53(d, 2H, CH.sub.2), 3.61(t,                1H,                                                                            CH), 3.82(m, 4H, CH), 3.87(s, 6H, OCH.sub.3), 6.16(s,                          1H, pyrimidine), 7.48(dd, 1H, pyridine), 8.14(dd, 1H,                          pyridine), 8.69(dd, 1H, pyridine).                                      509    δ: 3.25(s, 3H, NCH.sub.3), 3.67(t, 2H, CH.sub.2), 3.71(t,                2H,                                                                            CH.sub.2), 3.94(s, 6H, OCH.sub.3), 6.19(s, 1H,                                 pyrimidine), 7.50(dd, Jca=4.8, Jcb=7.8, 1H,                                    pyridine), 8.18(dd, Jba=1.5, Jbc=7.8, 1H, pyridine),                           8.72(dd, Jab=1.5, Jac=4.8, 1H, pyridine).                               510    δ: 1.77(s, 3H, CH.sub.3), 3.80(s, 6H, OCH.sub.3), 3.98(d,                2H,                                                                            N--CH.sub.2), 4.90(s, 2H, ═CH.sub.2), 5.70(d, 1H,                          OH), 5.85(s, 1H, pyrimidine), 6.8(d, 1H, OCH), 7.2-                            7.5(m, 1H, pyridine), 7.8-8.05(d, 1H, pyridine), 8.4-                          8.6(d, 1H, pyridine).                                                   511    δ: 0.18(s, 9H, Si(CH.sub.3).sub.3), 3.47(s, 3H,                          N--CH.sub.3),                                                                  3.90(s, 6H, OCH.sub.3), 4.20(s, 2H, CH.sub.2), 5.88(s,                         1H, pyrimidine C--H), 7.04(s, 1H, thiophene C--H),                             7.17(s, 5H, phenyl).                                                    512    δ: 0.12(s, 9H, Si(CH.sub.3).sub.2), 1.24(s, 9H, O-t-Bu),                 3.38(s,                                                                        3H, N--CH.sub.3), 3.84(s, 6H, OCH.sub.3), 5.83(s, 1H,                          pyrimidine C--H), 6.20(s, 1H, CH--O), 7.05(s, 5H,                              phenyl), 7.37(s, 1H, thiophene C--H).                                   513    δ: 0.75-1.15(t, 3H, CH.sub.3), 1.15-1.70(m, 6H, CH.sub.2),               2.25-2.70(m, 2H, OCH, OH), 3.45-4.00(m, 2H, NCH.sub.2),                        3.85(s, 6H, OCH.sub.3), 5.85(s, 1H, pyrimidine), 6.80(s, 1H,                   OCH), 7.30-8.80(m, 4H, pyridine, NH).                                   514    δ: 0.90(t, 3H, CH.sub.3), 1.10-1.67(m, 9H, CH.sub.2,                     CH.sub.3), 3.85(s, 6H, OCH.sub.3), 4.10(m, 1H, NCH), 5.90(s,                   1H, pyrimidine), 5.94(d, 1H, OH), 6.80(d, 1H, OCH),                            7.28-8.66(m, 4H, pyridine, NH).                                         515    δ: 1.06(m, 3H, CH.sub.3), 2.30(m, 1H, ═CH), 3.90(s, 6H,              OCH.sub.3), 3.92(m, 1H, NCH), 5.85(s, 1H, pyrimidine),                         5.95(s, 1H, OH), 6.95(s, 1H, OCH), 7.20-8.70(m, 4H,                            pyridine, NH).                                                          516    δ: 0.95(t, 3H, CH.sub.3), 1.50(q, 2H, CH.sub.2), 3.62(m,                 2H,                                                                            NCH.sub.2), 3.85(s, 6H, OCH.sub.3), 3.87(m, 1H, OCH),                          5.35(d, 1H, OH), 5.85(s, 1H, pyrimidine), 6.75(d, 1H,                          OCH), 7.30-8.80(m, 4H, pyridine, NH).                                   517    δ: 1.00-2.25(m, 10H, CH.sub.2), 3.85(s, 6H, OCH.sub.3),                  3.98(m, 1H, NCH), 5.85(s, 1H, pyrimidine), 5.88(d, 1H,                         OH), 6.68(d, 1H, OCH), 7.20-8.60(m, 4H, pyridine,                              NH).                                                                    518    δ: 3.78(s, 6H, OCH.sub.3), 6.40(s, 1H, pyrimidine),                      7.78(dd,                                                                       Jca=4.7, Jcb=7.7, 1H, pyridine), 8.17(dd, Jbc=                                 7.6, Jba=1.5, 1H, pyridine), 8.91(dd, Jac=4.7,                                 Jab=1.5, 1H, pyridine).                                                 519    δ: 2.12(m, 2H, CH.sub.2), 3.44(m, 2H, NCH.sub.2), 3.84(s,                6H,                                                                            OCH.sub.3), 4.00(m, 2H, NCH.sub.2), 4.87(s, 1H, OH),                           5.85(s, 1H, pyrimidine), 6.77(s, 1H, OCH), 6.90-8.68(m,                        7H, pyridine, imidazole, NH).                                           523    δ: 1.33(t, 3H, CH.sub.3), 3.85(s, 6H, OCH.sub.3), 4.14(s,                2H,                                                                            CH.sub.2), 4.40(q, 2H, OCH.sub.2), 5.87(s, 1H,                                 pyrimidine H), 7.35(d, 1H, pyridine H), 8.33(d, 1H,                            pyridine H).                                                            530    δ: 0.50(s, 9H, Si(CH.sub.3).sub.3), 3.40(s, 3H, NCH.sub.3),              3.85(s, 6H, OCH.sub.3), 4.10(s, 2H, CH.sub.2),                                 5.83(s, 1H, pyrimidine), 7.00-7.40(m, 5H, benzene).                     532    δ: 3.01-3.50(m, 2H, CH.sub.2 OH), 3.59-3.61(m, 4H,                       OCH.sub.2), 3.71-3.73(m, 2H, CH.sub.2 N), 3.99(s,                              6H, OCH.sub.3), 5.76(br s, 3H, NH), 6.08(s, 1H,                                pyrimidine), 7.27-7.31(m, 1H, aromatic), 7.45-                                 7.51(m, 2H, aromatic).                                                  553    δ: 1.41-1.46(t, 3H, CH.sub.3), 3.89(s, 6H, OCH.sub.3),                   4.47-4.52(q, 2H, OCH.sub.2), 5.93(s, 1H, CHBr), 6.52(s, 1H,                    pyrimidine), 8.35(d, 1H, J=5.25 Hz, pyridine), 8.83(s,                         1H, J=5.25 Hz, pyridine).                                               562    δ: 2.5(s, 3H, CH.sub.3), 3.9(s, 6H, OCH.sub.3), 5.9(s, 1H,               C HOH), 6.2(s, 1H, pyrimidine), 7.3(d, 1H, J=12 Hz,                            pyridine), 8.3(d, 1H, J=12 Hz, pyridine).                               571    δ: 1.26(t, 3H, CH.sub.3), 3.33(s, 3H, NCH.sub.3), 3.94(s,                6H,                                                                            OCH.sub.3), 4.11(s, 2H, NCH.sub.2), 4.25(q, 2H, OCH.sub.2),                    6.15(s, 1H, pyrimidine), 7.51(dd, Jca=4.8, ;Jcb=7.6,                           1H, pyridine), 8.10(dd, Jbc=7.7, Jab=1.6, 1H,                                  pyridine), 8.65(dd, Jac=4.8, Jab=1.6, 1H, pyridine).                    622    δ: 0.84(t, 3H, CH.sub.3), 1.08(d, 3H, CH.sub.3), 1.56(m,                 2H,                                                                            CH.sub.2), 3.89(s, 6H, OCH.sub.3), 4.78(m, 1H, CH), 6.13(s,                    1H, pyrimidine), 7.62(dd, Jca=4.8, Jcb=7.6, 1H,                                pyridine), 7.94(dd, Jba=1.6, Jbc=7.6, 1H, pyridine),                           8.85(dd, Jab=1.6, Jac=4.8, 1H, pyridine).                               625    δ: 0.87(t, 3H, CH.sub.3), 1.28(m, 2H, CH.sub.2), 1.54(m,                 2H,                                                                            CH.sub.2), 3.89(s, 6H, OCH.sub.3), 4.09(t, 2H, OCH.sub.2),                     6.13(s, 1H, pyrimidine), 7.62(dd, Jca=4.7, Jcb=7.7, 1H,                        pyridine), 7.99(dd, Jba=1.5, Jbc=7.7, 1H, pyridine),                           8.84(dd, Jab=1.5, Jac=4.17, 1H, pyridine).                              ______________________________________                                     

What is claimed is:
 1. A compound of formula I ##STR353## wherein ring system A is naphthyl R is cyano, formyl, CX₁ X₂ X₃, a ketone forming group, a carboxyl group which may be in the form of the free acid or in ester or salt form, a thiocarboxyl group which may be in the form of the free acid or in ester form, a carbamoyl group or a mono- or di-substituted carbamoyl group, hydroxyalkyl, hydroxybenzyl, --CH═NOH, --CH═NO-lower alkyl, the group --CH₂ --O--C(O)-- which bridges adjacent carbon atoms in ring A,Y₁, Y₂ and Y₃ are attached to carbon atoms and are independently hydrogen, halogen, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylsulfonyloxy, dialkylsulfamoyloxy, alkylsulfonyl, alkylsulfinyl, dialkylcarbamoyloxy, alkylthio, alkenylthio or alkynylthio each of which may in turn be substituted by 1 to 6 halogen atoms; dialkoxymethyl, conjugated alkoxy, hydroxyalkyl, carboxyl, acyl, acylalkyl, acyloxy, acyloxyalkyl, trialkylsilyloxy, trialkylsilyl, cyano, nitro, amino or substituted amino, aminosulfonyl; cycloalkyl, aryl, aralkyl, aralkenyl, aralkynyl, aryloxy, aralkoxy, arylsulfonyl, arylsulfinyl, arylthio or aralkylthio, each of which may be substituted by one to three substituents selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, cyano, alkylthio, acyl, amino or substituted amino; a group ##STR354## wherein R' is hydrogen, lower alkyl, or lower alkoxy; or Y₁ and R taken together on adjacent carbon atoms form a bridge having the formula ##STR355## wherein E is a 1 to 3 membered linking group with elements selected from methylene, substituted methylene, ##STR356## and oxygen; or Y₁ and Y₂ taken together on adjacent carbon atoms form a 3- to 5-membered bridge comprised of elements selected from methylene, substituted methylene, ##STR357## oxygen, and ##STR358## R₁, R₃ ' and R₃ are independently hydrogen; halogen; alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkenylthio or alkynylthio, each of which may in turn be substituted by 1 to 6 halogen atoms; cycloalkyl, heterocycloalkoxy, aryloxy, aralkoxy or aralkylthio each of which may be substituted by 1 to 3 substituents selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, cyano, alkylthio, acyl, amino or substituted amino; aminoxy; substituted aminoxy; iminoxy; substituted iminoxy; amino; substituted amino; amido; substituted amido; alkylsulfonylmethyl; cyano; nitro; or --C--Y₄ wherein Y₄ is hydrogen, lower alkyl, lower alkoxy, hydroxy or unsubstituted or substituted phenyl; R₄ is as defined for Y₁ except for hydrogen; X and Y each is independently hydrogen, hydroxy, halogen, cyano, alkyl, alkoxy, alkoxycarbonyl, alkoxycarbonyloxy, hydroxyalkyl, haloalkyl, acyl, acyloxy, carbamoyl, carbamoyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl or alkylsulfonyloxy; aryl, aryloxy, arylS(O)p, aralkyl, aralkoxy, aralkS(O)p, arylsulphonyloxy, each of which may in turn be substituted by 1 to 3 substituents selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, cyano, alkylthio, acyl; amino, substituted amino or together represent ═O, ═S, ═NH, ═NOR₁₂ or ═CR₁₃ R₁₄ ; or X and R together may form a bridge having the formula --O--E--, ##STR359## wherein the carbonyl is attached to A, E is defined above and R₂ represents hydrogen, hydroxy, alkyl, haloalkyl, alkoxyalkyl, alkoxy, aralkoxy, unsubstituted or substituted aryl, unsubstituted or substituted aralkyl or is as otherwise defined for R₇ hereinafter; P is 0, 1 or 2; X₁, X₂ and X₃ are independently hydrogen, hydroxy, alkoxy, alkylthio, hydroxyalkyl or hydroxybenzyl whereby at least one of X₁, X₂ and X₃ is other than hydrogen; or X₃ represents hydrogen and X₁ and X₂ together form a four or five membered bridge comprising elements selected from --O(CH₂)_(n') O--, ##STR360## and --S(CH₂)_(n') S--; R₁₂ is hydrogen or alkyl, R₁₃ and R₁₄ are independently hydrogen, alkyl or halogen, m is one or two, n is zero, one or two, and n' is two or three.
 2. A compound according to claim 1 wherein R is other than formyl, a carboxyl group which may be in the form of the free acid or in ester or salt form, a thiocarboxyl group which may be in the form the free acid or in ester form or the group CX₁ X₂ X₃.
 3. A compound according to claim 1 wherein both of X and Y are other than hydrogen.
 4. A compound according to claim 1 wherein one of X and Y is other than hydrogen, fluorine, chlorine, methyl, hydroxy, cyano, carbamoyl, methylcarbamoyl, dimethylcarbamoyl or COOR₃₅, wherein R₃₅ is C₁₋₃ alkyl, C₂₋₅ haloalkyl, C₃₋₅ alkenyl, C₃₋₅ alkynyl, C₂₋₅ alkoxyalkyl, or benzyl optionally substituted by methyl, methoxy, methylthio, trifluoromethyl, halogen or nitro.
 5. A compound according to claim 1 wherein R is a carboxyl group which may be in the form of the free acid or in ester or salt form, a thiocarboxyl group which may be in the form of the free acid or in ester form, a carbamoyl group or a mono- or di-substituted carbamoyl group;Y₁, Y₂ and Y₃ are independently hydrogen, halogen, alkyl and alkoxy; R₁, R_(3') and R₃ are independently hydrogen, halogen, alkyl, alkoxy, aryloxy and aralkoxy and X and Y each is independently hydrogen, hydroxy, cyano, alkoxy, or acyloxy or together represent ═O.
 6. A compound according to claim 5 wherein X and Y together represent ═O.
 7. A compound according to claim 5 wherein R₁, R_(3') and R₃ independently are hydrogen and alkoxy.
 8. A compound according to claim 5 wherein R is a carboxyl group which may be in the form of the free acid or in ester or salt form.
 9. A compound according to claim 5 wherein Y₁, Y₂ and Y₃ are hydrogen; X and Y together represent ═O; R₁, R_(3') and R₃ independently are hydrogen and alkoxy; and R is a carboxyl group which may be in the form of the free acid or in ester or salt form.
 10. A compound according to claim 5 wherein R is COOR₅ wherein R₅ is hydrogen, alkyl, COO⁺ Ma⁻ wherein Ma⁻ is an alkali metal or ammonium cation.
 11. A compound according to claim 1 having the formula ##STR361## wherein R is a carboxyl group which may be in the form of the free acid or in ester or salt form, a thiocarboxyl group which may be in the form of the free acid or in ester form, a carbamoyl group or a mono- or di-substituted carbamoyl group;Y₁, Y₂ and Y₃ are independently hydrogen, halogen, alkyl and alkoxy; R₁, R_(3') and R₃ are independently hydrogen, halogen, alkyl, alkoxy, aryloxy and aralkoxy and X and Y each is independently hydrogen, hydroxy, cyano, alkoxy, or acyloxy or together represent ═O.
 12. A compound according to claim 1 having the formula ##STR362## wherein R is a carboxyl group which may be in the form of the free acid or in ester or salt form, a thiocarboxyl group which may be in the form of the free acid or in ester form, a carbamoyl group or a mono- or di-substituted carbamoyl group;Y₁, Y₂ and Y₃ are independently hydrogen, halogen, alkyl and alkoxy; R₁, R_(3') and R₃ are independently hydrogen, halogen, alkyl, alkoxy, aryloxy and aralkoxy and X and Y each is independently hydrogen, hydroxy, cyano, alkoxy, or acyloxy or together represent ═O.
 13. A compound according to claim 1 having the formula ##STR363## wherein R is a carboxyl group which may be in the form of the free acid or in ester or salt form, a thiocarboxyl group which may be in the form of the free acid or in ester form, a carbamoyl group or a mono- or di-substituted carbamoyl group;Y₁, Y₂ and Y₃ are independently hydrogen, halogen, alkyl and alkoxy; R₁, R₃, and R₃ are independently hydrogen, halogen, alkyl, alkoxy, aryloxy and aralkoxy and X and Y each is independently hydrogen, hydroxy, cyano, alkoxy, or acyloxy or together represent ═O.
 14. A herbicidal composition comprising an herbicidally effective amount of a compound according to claim
 1. 15. A method for combatting weeds which comprises applying thereto or to a locus thereof an herbicidally effective amount of a compound according to claim
 1. 